Pafah1b1

Summary

Gene Symbol: Pafah1b1
Description: platelet-activating factor acetylhydrolase 1b, regulatory subunit 1
Alias: LIS1, platelet-activating factor acetylhydrolase IB subunit alpha, LIS-1, PAF acetylhydrolase 45 kDa subunit, PAF-AH 45 kDa subunit, PAF-AH alpha, PAF-AH beta, PAFAH alpha, lissencephaly-1 protein, platelet-activating factor acetylhydrolase beta subunit (PAF-AH beta), platelet-activating factor acetylhydrolase, isoform 1b, subunit 1, platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit 45kDa
Species: rat
Products:     Pafah1b1

Top Publications

  1. Dujardin D, Barnhart L, Stehman S, Gomes E, Gundersen G, Vallee R. A role for cytoplasmic dynein and LIS1 in directed cell movement. J Cell Biol. 2003;163:1205-11 pubmed
    ..We now find that dynein and its regulators dynactin and LIS1 localize to the leading cell cortex during this process...
  2. 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...
  3. 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...
  4. 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...
  5. 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...
  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. 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...
  8. 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...
  9. 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...

More Information

Publications50

  1. Tai C, Dujardin D, Faulkner N, Vallee R. Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. J Cell Biol. 2002;156:959-68 pubmed
    Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, LIS1 participates in cytoplasmic dynein-mediated nuclear migration...
  2. Faulkner N, Dujardin D, Tai C, Vaughan K, O Connell C, Wang Y, et al. A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nat Cell Biol. 2000;2:784-91 pubmed
    Mutations in the LIS1 gene cause gross histological disorganization of the developing human brain, resulting in a brain surface that is almost smooth...
  3. Cardoso C, Leventer R, Matsumoto N, Kuc J, Ramocki M, Mewborn S, et al. The location and type of mutation predict malformation severity in isolated lissencephaly caused by abnormalities within the LIS1 gene. Hum Mol Genet. 2000;9:3019-28 pubmed
    ..The LIS1 gene on 17p13.3 encodes a 45 kDa protein named PAFAH1B1 containing seven WD40 repeats...
  4. Lo Nigro C, Chong C, Smith A, Dobyns W, Carrozzo R, Ledbetter D. Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Hum Mol Genet. 1997;6:157-64 pubmed
    ..A gene containing beta-transducin like repeats, now known as LIS1, was previously mapped to the ILS/MDS chromosome region on 17p13.3...
  5. 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...
  6. 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...
  7. 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...
  8. 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 ..
  9. Smith D, Niethammer M, Ayala R, Zhou Y, Gambello M, Wynshaw Boris A, et al. Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1. Nat Cell Biol. 2000;2:767-75 pubmed
    Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1 gene results in brain abnormalities, indicating that developing neurons are particularly sensitive to a reduction in Lis1 dosage...
  10. 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 ..
  11. 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...
  12. Tsai J, Chen Y, Kriegstein A, Vallee R. LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J Cell Biol. 2005;170:935-45 pubmed
    Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly...
  13. Morris S, Albrecht U, Reiner O, Eichele G, Yu Lee L. The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC. Curr Biol. 1998;8:603-6 pubmed
    ..Miller-Dieker syndrome (MDS) or isolated lissencephaly sequence (ILS) have a hemizygous deletion or mutation in the LIS1 gene [3,6]; both conditions are characterized by a smooth cerebral surface, a thickened cortex with four abnormal ..
  14. Gutiérrez P, Ackermann B, Vershinin M, McKenney R. Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive dynein-dynactin motility. J Biol Chem. 2017;292:12245-12255 pubmed publisher
    ..Lissencephaly-1 (LIS1) is a highly conserved dynein-regulatory factor that binds directly to the dynein motor domain, uncoupling the ..
  15. 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...
  16. Walser M, Hansen A, Svensson P, Jernas M, Oscarsson J, Isgaard J, et al. Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats. Growth Horm IGF Res. 2011;21:16-24 pubmed publisher
    ..These transcripts represent potential novel mechanisms by which GH can interact with the brain. ..
  17. 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...
  18. Grabham P, Seale G, Bennecib M, Goldberg D, Vallee R. Cytoplasmic dynein and LIS1 are required for microtubule advance during growth cone remodeling and fast axonal outgrowth. J Neurosci. 2007;27:5823-34 pubmed
    Recent evidence has implicated dynein and its regulatory factors dynactin and LIS1 in neuronal and non-neuronal cell migration...
  19. Caspi M, Atlas R, Kantor A, Sapir T, Reiner O. Interaction between LIS1 and doublecortin, two lissencephaly gene products. Hum Mol Genet. 2000;9:2205-13 pubmed
    Mutations in either LIS1 or DCX are the most common cause for type I lissencephaly. Here we report that LIS1 and DCX interact physically both in vitro and in vivo...
  20. Tsai J, Bremner K, Vallee R. Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci. 2007;10:970-9 pubmed
    ..RNA interference (RNAi) of the lissencephaly gene LIS1 (also known as PAFAH1b1) inhibits somal movement but not process extension of neural precursors in live brain slices...
  21. 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...
  22. Pletnikov M, Xu Y, Ovanesov M, Kamiya A, Sawa A, Ross C. PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation. Neurosci Res. 2007;58:234-44 pubmed
    ..are associated with altered sub-cellular distribution of endogenous DISC1 and ATF4, and decreased protein levels of LIS1. Thus, inducible expression of DISC1 in PC12 cell clones is a valuable in vitro model for further studying the ..
  23. Shmueli O, Cahana A, Reiner O. Platelet-activating factor (PAF) acetylhydrolase activity, LIS1 expression, and seizures. J Neurosci Res. 1999;57:176-84 pubmed
    Lissencephaly patients are born with severe brain malformations and suffer from recurrent seizures. LIS1, the gene mutated in isolated lissencephaly patients, is a subunit of the heterotrimeric cytosolic enzyme platelet-activating factor ..
  24. 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 ..
  25. 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...
  26. Lipska B, Peters T, Hyde T, Halim N, Horowitz C, Mitkus S, et al. Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Hum Mol Genet. 2006;15:1245-58 pubmed
    ..and elongation protein zeta-1 (FEZ1), platelet-activating factor acetylhydrolase, isoform Ib, PAFAH1B1 or lissencephaly 1 protein (LIS1) and nuclear distribution element-like (NUDEL)...
  27. Hebbar S, Mesngon M, Guillotte A, Desai B, Ayala R, Smith D. Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells. J Cell Biol. 2008;182:1063-71 pubmed publisher
    b>Lis1 and Ndel1 are essential for animal development. They interact directly with one another and with cytoplasmic dynein...
  28. McKenney R, Weil S, Scherer J, Vallee R. Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. J Biol Chem. 2011;286:39615-22 pubmed publisher
    ..Together these results reveal an unanticipated mechanism for preventing dual regulation of individual dynein molecules, and identify the IC as a nexus for regulatory interactions within the dynein complex. ..
  29. Sumigray K, Chen H, Lechler T. Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J Cell Biol. 2011;194:631-42 pubmed publisher
    ..These include Lis1 and Ndel1, which are centrosomal proteins that regulate microtubule organization and anchoring in other cell types...
  30. Nayernia K, Vauti F, Meinhardt A, Cadenas C, Schweyer S, Meyer B, et al. Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility. J Biol Chem. 2003;278:48377-85 pubmed
    b>Lis1 protein is the non-catalytic component of platelet-activating factor acetylhydrolase 1b (PAF-AH 1B) and associated with microtubular structures...
  31. 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 ..
  32. Guarda P, Vitale M. [A rare case of ileo-ileal intussusception secondary to adenocarcinoma of the small intestine in a 21-year-old adult]. Minerva Chir. 1991;46:985-7 pubmed
  33. Watanabe M, Aoki J, Manya H, Arai H, Inoue K. Molecular cloning of cDNAs encoding alpha1, alpha2, and beta subunits of rat brain platelet-activating factor acetylhydrolase. Biochim Biophys Acta. 1998;1401:73-9 pubmed
  34. 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 ..
  35. Shao C, Zhu J, Xie Y, Wang Z, Wang Y, Wang Y, et al. Distinct functions of nuclear distribution proteins LIS1, Ndel1 and NudCL in regulating axonal mitochondrial transport. Traffic. 2013;14:785-97 pubmed publisher
    ..Nuclear distribution (Nud) family proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein complex...
  36. Xing Z, Tang X, Gao Y, Da L, Song H, Wang S, et al. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function. Biochem Biophys Res Commun. 2011;409:193-9 pubmed publisher
    The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13...
  37. Manya H, Aoki J, Watanabe M, Adachi T, Asou H, Inoue Y, et al. Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain. J Biol Chem. 1998;273:18567-72 pubmed
    ..The latter is a product of the LIS1 gene, which is defective in the Miller-Dieker syndrome, a form of lissencephaly...
  38. 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 ..
  39. Taya S, Shinoda T, Tsuboi D, Asaki J, Nagai K, Hikita T, et al. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. J Neurosci. 2007;27:15-26 pubmed
    ..DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3epsilon. 14-3-3epsilon is involved in the proper localization of NUDEL and LIS1 in axons...
  40. 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...
  41. 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...