Pafah1b1

Summary

Gene Symbol: Pafah1b1
Description: platelet-activating factor acetylhydrolase, isoform 1b, subunit 1
Alias: LIS-1, Lis1, MMS10-U, Mdsh, Ms10u, Pafaha, platelet-activating factor acetylhydrolase IB subunit alpha, PAF acetylhydrolase 45 kDa subunit, PAF-AH 45 kDa subunit, PAF-AH alpha, PAFAH alpha, Pafaha/Lis1, lissencephaly-1 protein, platelet-activating factor acetylhydrolase 1b, regulatory subunit 1, platelet-activating factor acetylhydrolase, isoform 1b, beta1 subunit, truncated form platelet-activating factor acetylhydrolase 45kD subunit
Species: mouse
Products:     Pafah1b1

Top Publications

  1. Yan W, Assadi A, Wynshaw Boris A, Eichele G, Matzuk M, Clark G. Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis. Proc Natl Acad Sci U S A. 2003;100:7189-94 pubmed
    ..PAF acetylhydrolase 1b (PAFAH1B) hydrolyzes PAF and is composed of three subunits [the lissencephaly (LIS1) protein and alpha1 and alpha2 subunits] and structurally resembles a GTP-hydrolyzing protein...
  2. Gambello M, Darling D, Yingling J, Tanaka T, Gleeson J, Wynshaw Boris A. Multiple dose-dependent effects of Lis1 on cerebral cortical development. J Neurosci. 2003;23:1719-29 pubmed
    Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form of cortical dysplasia hypothesized to result from abnormal neuronal migration...
  3. Moon H, Youn Y, Pemble H, Yingling J, Wittmann T, Wynshaw Boris A. LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein complex. Hum Mol Genet. 2014;23:449-66 pubmed publisher
    Heterozygous LIS1 mutations are responsible for the human neuronal migration disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many organisms throughout evolution...
  4. Derewenda U, Tarricone C, Choi W, Cooper D, Lukasik S, Perrina F, et al. The structure of the coiled-coil domain of Ndel1 and the basis of its interaction with Lis1, the causal protein of Miller-Dieker lissencephaly. Structure. 2007;15:1467-81 pubmed
    ..functions are dependent on their interactions with the retrograde microtubule motor dynein and with its regulator Lis1--a product of the causal gene for isolated lissencephaly sequence (ILS) and Miller-Dieker lissencephaly...
  5. Zhang G, Assadi A, McNeil R, Beffert U, Wynshaw Boris A, Herz J, et al. The Pafah1b complex interacts with the reelin receptor VLDLR. PLoS ONE. 2007;2:e252 pubmed
    ..Lis1, the product of the Pafah1b1 gene, is a component of the brain platelet-activating factor acetylhydrolase 1b (Pafah1b) complex, and binds to ..
  6. Sudarov A, Gooden F, Tseng D, Gan W, ROSS M. Lis1 controls dynamics of neuronal filopodia and spines to impact synaptogenesis and social behaviour. EMBO Mol Med. 2013;5:591-607 pubmed publisher
    LIS1 (PAFAH1B1) mutation can impair neuronal migration, causing lissencephaly in humans. LIS1 loss is associated with dynein protein motor dysfunction, and disrupts the actin cytoskeleton through disregulated RhoGTPases...
  7. Pawlisz A, Feng Y. Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes. PLoS Biol. 2011;9:e1001172 pubmed publisher
    ..Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophin/dystroglycan glycoprotein complex (DGC)...
  8. Sasaki S, Mori D, Toyo oka K, Chen A, Garrett Beal L, Muramatsu M, et al. Complete loss of Ndel1 results in neuronal migration defects and early embryonic lethality. Mol Cell Biol. 2005;25:7812-27 pubmed
    ..NDEL1 was identified as a protein interacting with LIS1, the protein product of a gene mutated in the lissencephaly...
  9. Pramparo T, Libiger O, Jain S, Li H, Youn Y, Hirotsune S, et al. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects. PLoS Genet. 2011;7:e1001331 pubmed publisher
    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly...

More Information

Publications79

  1. Toyo oka K, Sasaki S, Yano Y, Mori D, Kobayashi T, Toyoshima Y, et al. Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum Mol Genet. 2005;14:3113-28 pubmed
    b>LIS1 is mutated in the human neuronal migration defect lissencephaly and along with NDEL1 (formerly NUDEL) participates in the regulation of cytoplasmic dynein function during neuronal development...
  2. Pramparo T, Youn Y, Yingling J, Hirotsune S, Wynshaw Boris A. Novel embryonic neuronal migration and proliferation defects in Dcx mutant mice are exacerbated by Lis1 reduction. J Neurosci. 2010;30:3002-12 pubmed publisher
    Heterozygous LIS1 mutations and males with loss of the X-linked DCX result in lissencephaly, a neuronal migration defect...
  3. Greenwood J, Wang Y, Estrada R, Ackerman L, Ohara P, Baraban S. Seizures, enhanced excitation, and increased vesicle number in Lis1 mutant mice. Ann Neurol. 2009;66:644-53 pubmed publisher
    In humans, abnormal neuronal migration and severe neuronal disorganization resulting from Lis1 (lissencephaly) haploinsufficiency contributes to cognitive impairment and seizures early in life...
  4. Coquelle F, Caspi M, Cordelières F, Dompierre J, Dujardin D, Koifman C, et al. LIS1, CLIP-170's key to the dynein/dynactin pathway. Mol Cell Biol. 2002;22:3089-102 pubmed
    ..b>LIS1, a protein implicated in brain development, acts in several processes mediated by the dynein/dynactin pathway by ..
  5. Cahana A, Escamez T, Nowakowski R, Hayes N, Giacobini M, von Holst A, et al. Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization. Proc Natl Acad Sci U S A. 2001;98:6429-34 pubmed
    Lissencephaly is a severe brain malformation in humans. To study the function of the gene mutated in lissencephaly (LIS1), we deleted the first coding exon from the mouse Lis1 gene...
  6. Niethammer M, Smith D, Ayala R, Peng J, Ko J, Lee M, et al. NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron. 2000;28:697-711 pubmed
    Disruption of one allele of the LIS1 gene causes a severe developmental brain abnormality, type I lissencephaly...
  7. Feng Y, Olson E, Stukenberg P, Flanagan L, Kirschner M, Walsh C. LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome. Neuron. 2000;28:665-79 pubmed
    b>LIS1, a microtubule-associated protein, is required for neuronal migration, but the precise mechanism of LIS1 function is unknown...
  8. Pawlisz A, Mutch C, Wynshaw Boris A, Chenn A, Walsh C, Feng Y. Lis1-Nde1-dependent neuronal fate control determines cerebral cortical size and lamination. Hum Mol Genet. 2008;17:2441-55 pubmed publisher
    ..Haploinsufficiency of human LIS1 results in type I lissencephaly (smooth brain) with severely reduced surface area and laminar organization of the ..
  9. Shen Y, Li N, Wu S, Zhou Y, Shan Y, Zhang Q, et al. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev Cell. 2008;14:342-53 pubmed publisher
    ..Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel. ..
  10. Albrecht U, Abu Issa R, Ratz B, Hattori M, Aoki J, Arai H, et al. Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuronal migration and platelet-activating factor. Dev Biol. 1996;180:579-93 pubmed
    A hemizygous deletion of LIS1, the gene encoding alphaLis1 protein, causes Miller-Dieker syndrome (MDS)...
  11. Kholmanskikh S, Koeller H, Wynshaw Boris A, Gomez T, Letourneau P, Ross M. Calcium-dependent interaction of Lis1 with IQGAP1 and Cdc42 promotes neuronal motility. Nat Neurosci. 2006;9:50-7 pubmed
    b>Lis1 gene defects impair neuronal migration, causing the severe human brain malformation lissencephaly...
  12. Yamada M, Yoshida Y, Mori D, Takitoh T, Kengaku M, Umeshima H, et al. Inhibition of calpain increases LIS1 expression and partially rescues in vivo phenotypes in a mouse model of lissencephaly. Nat Med. 2009;15:1202-7 pubmed publisher
    Lissencephaly is a devastating neurological disorder caused by defective neuronal migration. LIS1 (official symbol PAFAH1B1, for platelet-activating factor acetylhydrolase, isoform 1b, subunit 1) was identified as the gene mutated in ..
  13. Yingling J, Youn Y, Darling D, Toyo oka K, Pramparo T, Hirotsune S, et al. Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division. Cell. 2008;132:474-86 pubmed publisher
    ..Here we report that Lis1 is essential for precise control of mitotic spindle orientation in both neuroepithelial stem cells and radial glial ..
  14. Nguyen M, Shu T, Sanada K, Lariviere R, Tseng H, Park S, et al. A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol. 2004;6:595-608 pubmed
    ..Furthermore, variations in levels of NUDEL correlate with disease progression and NF defects in a mouse model of neurodegeneration. Thus, NUDEL contributes to the integrity of CNS neurons by regulating NF assembly. ..
  15. Assadi A, Zhang G, Beffert U, McNeil R, Renfro A, Niu S, et al. Interaction of reelin signaling and Lis1 in brain development. Nat Genet. 2003;35:270-6 pubmed
    Loss-of-function mutations in RELN (encoding reelin) or PAFAH1B1 (encoding LIS1) cause lissencephaly, a human neuronal migration disorder...
  16. Toyo oka K, Shionoya A, Gambello M, Cardoso C, Leventer R, Ward H, et al. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003;34:274-85 pubmed
    ..Mutations in PAFAH1B1 (the gene encoding LIS1) are responsible for ILS and contribute to MDS, but the genetic causes of the greater ..
  17. Youn Y, Pramparo T, Hirotsune S, Wynshaw Boris A. Distinct dose-dependent cortical neuronal migration and neurite extension defects in Lis1 and Ndel1 mutant mice. J Neurosci. 2009;29:15520-30 pubmed publisher
    Haploinsufficiency of LIS1 results in lissencephaly, a human neuronal migration disorder...
  18. Sasaki S, Shionoya A, Ishida M, Gambello M, Yingling J, Wynshaw Boris A, et al. A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system. Neuron. 2000;28:681-96 pubmed
    Mutations in mammalian Lis1 (Pafah1b1) result in neuronal migration defects. Several lines of evidence suggest that LIS1 participates in pathways regulating microtubule function, but the molecular mechanisms are unknown...
  19. Kholmanskikh S, Dobrin J, Wynshaw Boris A, Letourneau P, Ross M. Disregulated RhoGTPases and actin cytoskeleton contribute to the migration defect in Lis1-deficient neurons. J Neurosci. 2003;23:8673-81 pubmed
    Lissencephaly is a severe brain malformation caused by impaired neuronal migration. Lis1, a causative gene, functions in an evolutionarily conserved nuclear translocation pathway regulating dynein motor and microtubule dynamics...
  20. Kim M, Cooper D, Oleksy A, Devedjiev Y, Derewenda U, Reiner O, et al. The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications. Structure. 2004;12:987-98 pubmed
    Mutations in the Lis1 gene result in lissencephaly (smooth brain), a debilitating developmental syndrome caused by the impaired ability of postmitotic neurons to migrate to their correct destination in the cerebral cortex...
  21. Koizumi H, Yamaguchi N, Hattori M, Ishikawa T, Aoki J, Taketo M, et al. Targeted disruption of intracellular type I platelet activating factor-acetylhydrolase catalytic subunits causes severe impairment in spermatogenesis. J Biol Chem. 2003;278:12489-94 pubmed
    ..is a phospholipase that consists of a dimer of two homologous catalytic subunits alpha1 and alpha2 as well as LIS1, a product of the causative gene for type I lissencephaly...
  22. Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim M, Derewenda Z, et al. Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. Neuron. 2004;44:809-21 pubmed
    Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder...
  23. Zhang X, Lei K, Yuan X, Wu X, Zhuang Y, Xu T, et al. SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron. 2009;64:173-87 pubmed publisher
    ..Although dynein, Lis1, and other cytoplasmic proteins are known for their roles in connecting microtubules to the nucleus during ..
  24. Hirotsune S, Fleck M, Gambello M, Bix G, Chen A, Clark G, et al. Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nat Genet. 1998;19:333-9 pubmed
    Heterozygous mutation or deletion of the beta subunit of platelet-activating factor acetylhydrolase (PAFAH1B1, also known as LIS1) in humans is associated with type I lissencephaly, a severe developmental brain disorder thought to result ..
  25. Paylor R, Hirotsune S, Gambello M, Yuva Paylor L, Crawley J, Wynshaw Boris A. Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice. Learn Mem. 1999;6:521-37 pubmed
    Heterozygous mutation or deletion of Pafab1b1 (LIS1) in humans is associated with syndromes with type 1 lissencephaly, a severe brain developmental disorder resulting from abnormal neuronal migration...
  26. Fleck M, Hirotsune S, Gambello M, Phillips Tansey E, Suares G, Mervis R, et al. Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly. J Neurosci. 2000;20:2439-50 pubmed
    ..and heterotopia throughout the granule cell and pyramidal cell layers of mice containing a heterozygous deletion of Lis1, a mouse model of human 17p13.3-linked lissencephaly...
  27. Singh K, Ge X, Mao Y, Drane L, Meletis K, Samuels B, et al. Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron. 2010;67:33-48 pubmed publisher
    ..Together, these data reveal that Dixdc1 integrates DISC1 into Wnt-GSK3beta/beta-catenin-dependent and -independent signaling pathways during cortical development and further delineate how DISC1 contributes to neuropsychiatric disorders. ..
  28. Mesngon M, Tarricone C, Hebbar S, Guillotte A, Schmitt E, Lanier L, et al. Regulation of cytoplasmic dynein ATPase by Lis1. J Neurosci. 2006;26:2132-9 pubmed
    Mutations in Lis1 cause classical lissencephaly, a developmental brain abnormality characterized by defects in neuronal positioning...
  29. Yano M, Hayakawa Yano Y, Mele A, Darnell R. Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Neuron. 2010;66:848-58 pubmed publisher
    ..Thus, Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease, and development. ..
  30. Belzil C, Asada N, Ishiguro K, Nakaya T, Parsons K, Pendolino V, et al. p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex. Biol Open. 2014;3:475-85 pubmed publisher
    ..We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis. ..
  31. Bradshaw N, Ogawa F, Antolin Fontes B, Chubb J, Carlyle B, Christie S, et al. DISC1, PDE4B, and NDE1 at the centrosome and synapse. Biochem Biophys Res Commun. 2008;377:1091-6 pubmed publisher
    ..Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D)...
  32. de Haan G, Bystrykh L, Weersing E, Dontje B, Geiger H, Ivanova N, et al. A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover. Blood. 2002;100:2056-62 pubmed
    ..Our data are consistent with the hypothesis that this isolated cell cycle QTL does not result from a mutation in a single gene but rather is a consequence of variable expression of a collection of highly linked genes. ..
  33. Jones D, Baraban S. Inhibitory inputs to hippocampal interneurons are reorganized in Lis1 mutant mice. J Neurophysiol. 2009;102:648-58 pubmed publisher
    ..In the disorganized hippocampal area CA1 of Lis1(+/-) mice, we initially observed a selective displacement of fast-spiking, parvalbumin-positive basket-type ..
  34. Mi Q, Zhou L, Grattan M, Wang Z, Sivilotti M, She J, et al. Characterization of PAF-AH Ib1 in NOD mice: PAF-AH may not be a candidate gene of the diabetes susceptibility Idd4.1 locus. Ann N Y Acad Sci. 2006;1079:147-52 pubmed
    ..PAF-AH activity does not differ in the pancreatic islets or spleen between NOD and B6 mice. Our findings suggest that PAF-AH Ib1 may not be a diabetes-susceptibility gene in the Idd4.1 sublocus. ..
  35. Jheng G, Hur S, Chang C, Wu C, Cheng J, Lee H, et al. Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration. Biochem Biophys Res Commun. 2018;497:869-875 pubmed publisher
    ..It requires complex processes of cell adhesion, cytoskeletal dynamics, and force generation. Lis1 plays an important role in the migration of neurons, fibroblasts and other cell types, and is essential for normal ..
  36. Sweeney K, Prokscha A, Eichele G. NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate coiled-coil proteins. Mech Dev. 2001;101:21-33 pubmed
    The LIS1-encoded protein (Lis1) plays a role in brain development because a hemizygous deletion or mutation of the human gene causes neuronal migration disorders, such as Miller-Dieker syndrome (MDS) or isolated lissencephaly sequence (..
  37. Sugitani Y, Nakai S, Minowa O, Nishi M, Jishage K, Kawano H, et al. Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Genes Dev. 2002;16:1760-5 pubmed
    ..These data indicate that Brn-1 and Brn-2 share roles in the production and positioning of neocortical neuron development. ..
  38. Stojanov T, O NEILL C. In vitro fertilization causes epigenetic modifications to the onset of gene expression from the zygotic genome in mice. Biol Reprod. 2001;64:696-705 pubmed
    ..Thus, IVF causes epigenetic modification in the normal pattern of expression of some but not all genes involved in normal embryo growth and survival. ..
  39. Jimenez Mateos E, Wandosell F, Reiner O, Avila J, Gonzalez Billault C. Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Biochem J. 2005;389:333-41 pubmed
    ..Therefore we have specifically analysed how two members of the MAP family, MAP1B and LIS1 (lissencephaly-related protein 1), interact with one another and participate in neuronal migration...
  40. Forte T, Oda M, Knoff L, Frei B, Suh J, Harmony J, et al. Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration. J Lipid Res. 1999;40:1276-83 pubmed
    ..2 nm particles. We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency. ..
  41. Bubier J, Wilcox T, Jay J, Langston M, Baker E, Chesler E. Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol. Front Behav Neurosci. 2016;10:1 pubmed publisher
    ..The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with ..
  42. Hippenmeyer S, Youn Y, Moon H, Miyamichi K, Zong H, Wynshaw Boris A, et al. Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration. Neuron. 2010;68:695-709 pubmed publisher
    ..The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex...
  43. Pedersen L, Rompolas P, Christensen S, Rosenbaum J, King S. The lissencephaly protein Lis1 is present in motile mammalian cilia and requires outer arm dynein for targeting to Chlamydomonas flagella. J Cell Sci. 2007;120:858-67 pubmed
    ..Classical lissencephaly is caused by mutations in LIS1, which encodes a WD-repeat protein involved in cytoplasmic dynein regulation, mitosis and nuclear migration...
  44. Hirotsune S, Pack S, Chong S, Robbins C, Pavan W, Ledbetter D, et al. Genomic organization of the murine Miller-Dieker/lissencephaly region: conservation of linkage with the human region. Genome Res. 1997;7:625-34 pubmed
    ..We have isolated the murine homologs of three genes located inside and outside the MDS region: Lis1, Mnt/Rox, and 14-3-3 epsilon...
  45. Cahana A, Jin X, Reiner O, Wynshaw Boris A, O NEILL C. A study of the nature of embryonic lethality in LIS1-/- mice. Mol Reprod Dev. 2003;66:134-42 pubmed
    ..We seek to define the nature of this demise. LIS1 (pafah1b1) is a 46 kDa protein with seven tryptophan-aspartate (WD) repeats...
  46. Ye S, Fowler T, Pavlos N, Ng P, Liang K, Feng Y, et al. LIS1 regulates osteoclast formation and function through its interactions with dynein/dynactin and Plekhm1. PLoS ONE. 2011;6:e27285 pubmed publisher
    ..Here, we have identified a novel interaction between microtubule regulator LIS1 and Plekhm1, a lysosome-associated protein implicated in osteoclast secretion...
  47. Liu J, Chen R, Marathe G, Febbraio M, Zou W, McIntyre T. Circulating platelet-activating factor is primarily cleared by transport, not intravascular hydrolysis by lipoprotein-associated phospholipase A2/ PAF acetylhydrolase. Circ Res. 2011;108:469-77 pubmed publisher
    ..Intravascular PAF has access to intracellular compartments. Inflammatory and proapoptotic phospholipids may accumulate in the circulation as transport is overwhelmed by substrates in hyperlipidemia. ..
  48. Lu J, Pierce M, Franklin A, Jilling T, Stafforini D, Caplan M. Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis. Pediatr Res. 2010;68:225-30 pubmed publisher
    ..In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and because preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. ..
  49. Moore K, Chen R, Cilluffo M, Golden J, Phelps P. Lis1 reduction causes tangential migratory errors in mouse spinal cord. J Comp Neurol. 2012;520:1198-211 pubmed publisher
    ..Lis1+/? (Pafah1b1) mice show defective lamination in the cerebral cortex and hippocampal formation, whereas homozygous mutations ..
  50. Reiner O, Albrecht U, Gordon M, Chianese K, Wong C, Gal Gerber O, et al. Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. J Neurosci. 1995;15:3730-8 pubmed
    ..b>LIS1, the gene defective in MDS, encodes a subunit of brain platelet-activating factor (PAF) acetylhydrolase which ..
  51. Chen X, Zhang J, Zhao J, Liu H, Sun X, Zhao M, et al. Lis1 is required for the expansion of hematopoietic stem cells in the fetal liver. Cell Res. 2014;24:1013-6 pubmed publisher
  52. Hebbar S, Guillotte A, Mesngon M, Zhou Q, Wynshaw Boris A, Smith D. Genetic enhancement of the Lis1+/- phenotype by a heterozygous mutation in the adenomatous polyposis coli gene. Dev Neurosci. 2008;30:157-70 pubmed
    Hemizygous Lis1 mutations cause type 1 lissencephaly, a neuronal migration disorder in humans. The Lis1+/- mouse is a model for lissencephaly; mice exhibit neuronal migration defects but are viable and fertile...
  53. Kurtz A, Zimmer A. The mouse homolog of the human Miller-Dieker chromosomal region (MDCR) maps to mouse chromosome 11 in close proximity to Mov9 and D11Nds1. Mamm Genome. 1995;6:145-6 pubmed
  54. Pandey J, Smith D. A Cdk5-dependent switch regulates Lis1/Ndel1/dynein-driven organelle transport in adult axons. J Neurosci. 2011;31:17207-19 pubmed publisher
    Lissencephaly is a human developmental brain abnormality caused by LIS1 haploinsufficiency. This disorder is in large part attributed to altered mitosis and migration in the developing brain...
  55. Sipe C, Liu L, Lee J, Grimsley Myers C, Lu X. Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization. Development. 2013;140:1785-95 pubmed publisher
    ..To elucidate the microtubule-mediated polarity pathway, we analyzed Lis1 function in the auditory sensory epithelium in the mouse...
  56. Jones D, Baraban S. Characterization of inhibitory circuits in the malformed hippocampus of Lis1 mutant mice. J Neurophysiol. 2007;98:2737-46 pubmed
    Heterozygous mutation or deletion of a lissencephaly gene (Lis1) in humans is associated with a severe disruption of cortical and hippocampal lamination, cognitive deficit, and severe seizures...
  57. Silver D, Watkins Chow D, Schreck K, Pierfelice T, Larson D, Burnetti A, et al. The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci. 2010;13:551-8 pubmed publisher
    ..rescue experiments showed that a key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis...
  58. McManus M, Nasrallah I, Pancoast M, Wynshaw Boris A, Golden J. Lis1 is necessary for normal non-radial migration of inhibitory interneurons. Am J Pathol. 2004;165:775-84 pubmed
    ..Mutations in, or deletions of, LIS1 are the most commonly recognized genetic anomaly associated with type I lissencephaly...
  59. Soukoulis V, Reddy S, Pooley R, Feng Y, Walsh C, Bader D. Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway. Proc Natl Acad Sci U S A. 2005;102:8549-54 pubmed
    b>LIS1 and nuclear distribution gene E (NudE) are partner proteins in a conserved pathway regulating the function of dynein and microtubules...
  60. Wang Y, Baraban S. Granule cell dispersion and aberrant neurogenesis in the adult hippocampus of an LIS1 mutant mouse. Dev Neurosci. 2007;29:91-8 pubmed
    ..Mutant mice with a heterozygous deletion of LIS1 show varying degrees of hippocampal abnormality and enhanced excitability...
  61. Bai J, Ramos R, Paramasivam M, Siddiqi F, Ackman J, LoTurco J. The role of DCX and LIS1 in migration through the lateral cortical stream of developing forebrain. Dev Neurosci. 2008;30:144-56 pubmed
    ..RNAi of DCX or LIS1 disrupted migration into amygdala and piriform cortex and caused many neurons to accumulate in the external and ..
  62. Valdés Sánchez L, Escámez T, Echevarria D, Ballesta J, Tabares Seisdedos R, Reiner O, et al. Postnatal alterations of the inhibitory synaptic responses recorded from cortical pyramidal neurons in the Lis1/sLis1 mutant mouse. Mol Cell Neurosci. 2007;35:220-9 pubmed
    Mutations in the mouse Lis1 gene produce severe alterations in the developing cortex. We have examined some electrophysiological responses of cortical pyramidal neurons during the early postnatal development of Lis/sLis1 mutant mice...
  63. Tokuoka S, Ishii S, Kawamura N, Satoh M, Shimada A, Sasaki S, et al. Involvement of platelet-activating factor and LIS1 in neuronal migration. Eur J Neurosci. 2003;18:563-70 pubmed
    ..PAF is produced in the brain from its precursor, and degraded by the enzyme PAF acetylhydrolase. LIS1 is a regulatory subunit of PAF acetylhydrolase, and is identical to a gene whose deletion causes the human neuronal ..
  64. Challen G, Gardiner B, Caruana G, Kostoulias X, Martinez G, Crowe M, et al. Temporal and spatial transcriptional programs in murine kidney development. Physiol Genomics. 2005;23:159-71 pubmed
  65. Hunt R, Dinday M, Hindle Katel W, Baraban S. LIS1 deficiency promotes dysfunctional synaptic integration of granule cells generated in the developing and adult dentate gyrus. J Neurosci. 2012;32:12862-75 pubmed publisher
    ..characterized by cognitive disability and refractory epilepsy, is often caused by heterozygous mutations in the LIS1 gene...
  66. Isumi H, Takashima S, Ikeda K, Mizuguchi M. Expression of a 45K subunit of platelet-activating factor acetylhydrolase in the developing mouse cerebellum. Anat Embryol (Berl). 1998;197:415-9 pubmed
    ..Our findings indicate that PAFAH expression is developmentally regulated and suggest its role in histogenetic processes in the cerebellar cortex other than neuronal migration. ..
  67. Kihara Y, Ishii S, Kita Y, Toda A, Shimada A, Shimizu T. Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor. J Exp Med. 2005;202:853-63 pubmed
    ..PAFR-KO macrophages reduced phagocytic activity and subsequent production of TNF-alpha. These results suggest that PAF plays a dual role in EAE pathology in the induction and chronic phases through the T cell-independent pathways. ..
  68. Moughamian A, Osborn G, Lazarus J, Maday S, Holzbaur E. Ordered recruitment of dynactin to the microtubule plus-end is required for efficient initiation of retrograde axonal transport. J Neurosci. 2013;33:13190-203 pubmed publisher
    ..In contrast, the +TIP Lis1 activates transport through a distinct mechanism and is required to maintain processive organelle transport along ..
  69. Peterfy M, Gyuris T, Grosshans D, Cuaresma C, Takacs L. Cloning and characterization of cDNAs and the gene encoding the mouse platelet-activating factor acetylhydrolase Ib alpha subunit/lissencephaly-1 protein. Genomics. 1998;47:200-6 pubmed
    ..Here we report the isolation and characterization of mouse Pafaha/Lis1 cDNAs and the corresponding Pafaha/Lis1 gene...
  70. Gardner A, Reichert E, Topham M, Stafforini D. Identification of a domain that mediates association of platelet-activating factor acetylhydrolase with high density lipoprotein. J Biol Chem. 2008;283:17099-106 pubmed publisher
    ..These findings contribute to our understanding of the mechanisms responsible for association of human PAF-AH with HDL and may facilitate future studies aimed at precisely determining the function of PAF-AH in each lipoprotein particle. ..