Genomes and Genes
Gene Symbol: Lama4
Description: laminin, alpha 4
Alias: laminin subunit alpha-4, laminin [a]4, laminin-14 subunit alpha, laminin-8 subunit alpha, laminin-9 subunit alpha
- Samuel M, Valdez G, Tapia J, Lichtman J, Sanes J. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS ONE. 2012;7:e46663 pubmed publisher..Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs. ..
- Ringelmann B, Roder C, Hallmann R, Maley M, Davies M, Grounds M, et al. Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice. Exp Cell Res. 1999;246:165-82 pubmed..These results have significant ramifications in the diagnosis of human merosin-negative CMD. ..
- Previtali S, Nodari A, Taveggia C, Pardini C, Dina G, Villa A, et al. Expression of laminin receptors in schwann cell differentiation: evidence for distinct roles. J Neurosci. 2003;23:5520-30 pubmed..These data suggest that the action of laminin is mediated by beta1 integrins during axonal sorting and by dystroglycan, alpha6beta1, and alpha6beta4 integrins during myelination. ..
- Patton B, Cunningham J, Thyboll J, Kortesmaa J, Westerblad H, Edstrom L, et al. Properly formed but improperly localized synaptic specializations in the absence of laminin alpha4. Nat Neurosci. 2001;4:597-604 pubmed..Thus, formation and localization of synaptic specializations are regulated separately, and alpha4beta2gamma1 (called laminin-9) is critical in the latter process. ..
- Rasi K, Hurskainen M, Kallio M, Stavén S, Sormunen R, Heape A, et al. Lack of collagen XV impairs peripheral nerve maturation and, when combined with laminin-411 deficiency, leads to basement membrane abnormalities and sensorimotor dysfunction. J Neurosci. 2010;30:14490-501 pubmed publisher..and the maturation of the nerve is permanently compromised, contrasting with the slow repair observed in Lama4-/- single knock-out mice...
- Miner J, Cunningham J, Sanes J. Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol. 1998;143:1713-23 pubmed..Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes. ..
- Lefebvre O, Sorokin L, Kedinger M, Simon Assmann P. Developmental expression and cellular origin of the laminin alpha2, alpha4, and alpha5 chains in the intestine. Dev Biol. 1999;210:135-50 pubmed
- Vaicik M, Blagajcevic A, Ye H, Morse M, Yang F, Goddi A, et al. The Absence of Laminin α4 in Male Mice Results in Enhanced Energy Expenditure and Increased Beige Subcutaneous Adipose Tissue. Endocrinology. 2018;159:356-367 pubmed publisherLaminin α4 (LAMA4) is located in the extracellular basement membrane that surrounds each individual adipocyte...
- Klaffky E, Williams R, Yao C, Ziober B, Kramer R, Sutherland A. Trophoblast-specific expression and function of the integrin alpha 7 subunit in the peri-implantation mouse embryo. Dev Biol. 2001;239:161-75 pubmed..These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm proliferation and differentiation. ..
- Fox M, Ho M, Smyth N, Sanes J. A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction. Neural Dev. 2008;3:24 pubmed publisher..Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction. ..
- Vaicik M, Thyboll Kortesmaa J, MovÃ©rare Skrtic S, Kortesmaa J, Soininen R, BergstrÃ¶m G, et al. Laminin Î±4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain. PLoS ONE. 2014;9:e109854 pubmed publisher..accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin Î±4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals...
- Ramakrishna S, Kim I, Petrovic V, Malin D, Wang I, Kalin T, et al. Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor. Dev Dyn. 2007;236:1000-13 pubmed..Foxm1 regulates expression of genes essential for the proliferation of cardiomyocytes during heart development. ..
- Court F, Hewitt J, Davies K, Patton B, Uncini A, Wrabetz L, et al. A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments. J Neurosci. 2009;29:3908-19 pubmed publisher..Other cell types may exploit dystroglycan complexes in similar fashions to create barriers and compartments. ..
- Lathia J, Patton B, Eckley D, Magnus T, Mughal M, Sasaki T, et al. Patterns of laminins and integrins in the embryonic ventricular zone of the CNS. J Comp Neurol. 2007;505:630-43 pubmed
- Yamashita H, Goto A, Kadowaki T, Kitagawa Y. Mammalian and Drosophila cells adhere to the laminin alpha4 LG4 domain through syndecans, but not glypicans. Biochem J. 2004;382:933-43 pubmed
- Yang D, Bierman J, Tarumi Y, Zhong Y, Rangwala R, Proctor T, et al. Coordinate control of axon defasciculation and myelination by laminin-2 and -8. J Cell Biol. 2005;168:655-66 pubmed..Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo. ..
- Warren K, Iwami D, Harris D, Bromberg J, Burrell B. Laminins affect T cell trafficking and allograft fate. J Clin Invest. 2014;124:2204-18 pubmed..Furthermore, reducing ?4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation. ..
- Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, et al. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med. 2009;15:519-27 pubmed publisher..The data indicate that T lymphocytes use mechanisms distinct from other immune cells to penetrate the endothelial basement membrane barrier, permitting specific targeting of this immune cell population. ..
- Sprenger C, Drivdahl R, Woodke L, Eyman D, Reed M, Carter W, et al. Senescence-induced alterations of laminin chain expression modulate tumorigenicity of prostate cancer cells. Neoplasia. 2008;10:1350-61 pubmed..This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer. ..
- Belvindrah R, Hankel S, Walker J, Patton B, Muller U. Beta1 integrins control the formation of cell chains in the adult rostral migratory stream. J Neurosci. 2007;27:2704-17 pubmed..In addition, we provide evidence that beta1 class integrins are required for the maintenance of the glial tubes and that defects in the glial tubes lead to the ectopic migration of neuroblasts into the surrounding tissue. ..
- Radmanesh F, Caglayan A, Silhavy J, Yilmaz C, Cantagrel V, Omar T, et al. Mutations in LAMB1 cause cobblestone brain malformation without muscular or ocular abnormalities. Am J Hum Genet. 2013;92:468-74 pubmed publisher..LAMB1 is localized to the pial basement membrane, suggesting that defective connection between radial glial cells and the pial surface mediated by LAMB1 leads to this malformation. ..
- Abrass C, Hansen K, Patton B. Laminin alpha4-null mutant mice develop chronic kidney disease with persistent overexpression of platelet-derived growth factor. Am J Pathol. 2010;176:839-49 pubmed publisher..null mutations in the majority of laminin chains lead to specific developmental abnormalities in the kidney, Lama4-/- mice have progressive glomerular and tubulointerstitial fibrosis...
- Gorfu G, Virtanen I, Hukkanen M, Lehto V, Rousselle P, Kenne E, et al. Laminin isoforms of lymph nodes and predominant role of alpha5-laminin(s) in adhesion and migration of blood lymphocytes. J Leukoc Biol. 2008;84:701-12 pubmed publisher..This study demonstrates a predominant role for alpha5-laminin(s) in blood lymphocyte biology and identifies LN laminins and their integrin receptors in blood lymphocytes. ..
- Stenzel D, Franco C, Estrach S, Mettouchi A, Sauvaget D, Rosewell I, et al. Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep. 2011;12:1135-43 pubmed publisher..Here we show that laminin ?4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo...
- Song J, Zhang X, Buscher K, Wang Y, Wang H, Di Russo J, et al. Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration. Cell Rep. 2017;18:1256-1269 pubmed publisher..Our data demonstrate that molecular information provided by basement membrane laminin 511 affects leukocyte extravasation both directly and indirectly by modulating endothelial barrier properties. ..
- Gersdorff N, Muller M, Otto S, Poschadel R, Hübner S, Miosge N. Basement membrane composition in the early mouse embryo day 7. Dev Dyn. 2005;233:1140-8 pubmed..In conclusion, laminin-1 might be the only laminin isoform in the early mouse embryo that, together with the other main BM components, nidogens, collagen type IV, and perlecan, is synthesized by all three germ layers. ..
- Ichikawa N, Kasai S, Suzuki N, Nishi N, Oishi S, Fujii N, et al. Identification of neurite outgrowth active sites on the laminin alpha4 chain G domain. Biochemistry. 2005;44:5755-62 pubmed..Taken together, the data suggest that the peptides from the laminin alpha4 chain G domain promote neurite outgrowth activity via a specific conformation. ..
- Yokoyama F, Suzuki N, Haruki M, Nishi N, Oishi S, Fujii N, et al. Cyclic peptides from the loop region of the laminin alpha 4 chain LG4 module show enhanced biological activity over linear peptides. Biochemistry. 2004;43:13590-7 pubmed..These results indicate that the activity of A4G82 is highly conformation-dependent, suggesting that the E-F loop structure is crucial for its biological activity. ..
- Blaess S, Graus Porta D, Belvindrah R, Radakovits R, Pons S, Littlewood Evans A, et al. Beta1-integrins are critical for cerebellar granule cell precursor proliferation. J Neurosci. 2004;24:3402-12 pubmed
- Miner J, Li C, Patton B. Laminins alpha2 and alpha4 in pancreatic acinar basement membranes are required for basal receptor localization. J Histochem Cytochem. 2004;52:153-6 pubmed..Importantly, these laminins were required for proper basal localization on acinar cells of two laminin receptors, dystroglycan and integrin alpha6beta4 . ..
- Hirohata S, Kusachi S, Kondo J, Sano I, Murakami M, Doi M, et al. Laminin alpha 1, alpha 2, alpha 4 and beta 1 chain mRNA expression in mouse embryonic, neonatal, and adult hearts. Jpn Heart J. 1997;38:281-9 pubmed..Laminin beta 1 was expressed in the hearts of mice at all stages examined. These results demonstrate that the laminin chain gene expression changes in the different developmental stages of the hearts of BALb/c mice. ..
- Miner J, Li C. Defective glomerulogenesis in the absence of laminin alpha5 demonstrates a developmental role for the kidney glomerular basement membrane. Dev Biol. 2000;217:278-89 pubmed
- Liu J, Mayne R. The complete cDNA coding sequence and tissue-specific expression of the mouse laminin alpha 4 chain. Matrix Biol. 1996;15:433-7 pubmed..3% identity. Northern blot analysis shows that mouse laminin alpha 4 is strongly expressed in heart, lung and skeletal muscle, with only limited expression in brain, spleen, liver, kidney and testes. ..
- Lopez Escobar B, De Felipe B, Sánchez Alcázar J, Sasaki T, Copp A, Ybot Gonzalez P. Laminin and integrin expression in the ventral ectodermal ridge of the mouse embryo: implications for regulation of BMP signalling. Dev Dyn. 2012;241:1808-15 pubmed publisher..Laminin532 could interact with Î±6-containing integrin to direct differentiation of the specialised VER cells from surface ectoderm. ..
- Liou G, Fei Y, Peachey N, Matragoon S, Wei S, Blaner W, et al. Early onset photoreceptor abnormalities induced by targeted disruption of the interphotoreceptor retinoid-binding protein gene. J Neurosci. 1998;18:4511-20 pubmed..These observations indicate that normal photoreceptor development and function are highly dependent on the early expression of IRBP, and that in the absence of IRBP there is a slowly progressive degeneration of retinal photoreceptors. ..
- van Lohuizen M, Tijms M, Voncken J, Schumacher A, Magnuson T, Wientjens E. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol Cell Biol. 1998;18:3572-9 pubmed..However, partial colocalization of Enx1 and Mph1 to subnuclear domains may point to more transient interactions between these complexes, in support of a bridging role for Enx1. ..
- Di Russo J, Luik A, Yousif L, Budny S, Oberleithner H, Hofschröer V, et al. Endothelial basement membrane laminin 511 is essential for shear stress response. EMBO J. 2017;36:183-201 pubmed publisher..This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries. ..
- Langen U, Pitulescu M, Kim J, Enriquez Gasca R, Sivaraj K, Kusumbe A, et al. Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat Cell Biol. 2017;19:189-201 pubmed publisher..Our work outlines fundamental principles of vessel formation and endothelial cell differentiation in the developing skeletal system. ..
- Lee K, Chand K, Hammond L, Lavidis N, Noakes P. Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression. Aging (Albany NY). 2017;9:880-899 pubmed publisher..These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging. ..
- Nunes A, Wuebbles R, Sarathy A, Fontelonga T, Deries M, Burkin D, et al. Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy. Hum Mol Genet. 2017;26:2018-2033 pubmed publisher..Our data reveal for the first time that dyW-/- mice exhibit a myogenesis defect already in utero. We propose that overactivation of JAK-STAT signaling is part of the mechanism underlying disease onset and progression in dyW-/- mice. ..
- Katagiri F, Ishikawa M, Yamada Y, Hozumi K, Kikkawa Y, Nomizu M. Screening of integrin-binding peptides from the laminin ?4 and ?5 chain G domain peptide library. Arch Biochem Biophys. 2012;521:32-42 pubmed publisher..Integrin binding peptides are useful for understanding laminin functions and have a potential to use for biomaterials and drug development. ..
- Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin L. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol. 2001;153:933-46 pubmed
- Nguyen N, Miner J, Pierce R, Senior R. Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung. Dev Biol. 2002;246:231-44 pubmed..Our finding of normal lung branching morphogenesis with abnormal lobar septation demonstrates that these processes are not obligatorily linked. ..
- Copp A, Carvalho R, Wallace A, Sorokin L, Sasaki T, Greene N, et al. Regional differences in the expression of laminin isoforms during mouse neural tube development. Matrix Biol. 2011;30:301-9 pubmed publisher..This information paves the way towards a mechanistic analysis of basement membrane laminin function during early neural tube development in mammals. ..
- Radakovits R, Barros C, Belvindrah R, Patton B, Muller U. Regulation of radial glial survival by signals from the meninges. J Neurosci. 2009;29:7694-705 pubmed publisher..Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size. ..
- Ichikawa Tomikawa N, Ogawa J, Douet V, Xu Z, Kamikubo Y, Sakurai T, et al. Laminin Î±1 is essential for mouse cerebellar development. Matrix Biol. 2012;31:17-28 pubmed publisher..A marked reduction in numbers of dendritic processes in Purkinje cells was observed in Lama1(CKO) mice. Together, these results indicate that Lama1 is required for cerebellar development and functions. ..
- Okazaki I, Suzuki N, Nishi N, Utani A, Matsuura H, Shinkai H, et al. Identification of biologically active sequences in the laminin alpha 4 chain G domain. J Biol Chem. 2002;277:37070-8 pubmed..These active peptides may be useful for defining of the molecular mechanism laminin-receptor interactions and laminin-mediated cellular signaling pathways. ..
- Salmivirta K, Sorokin L, Ekblom P. Differential expression of laminin alpha chains during murine tooth development. Dev Dyn. 1997;210:206-15 pubmed..These studies show that laminin networks in tooth epithelia form as a result of epithelial-mesenchymal interactions and that the molecular composition of the laminin networks varies drastically during development of tooth. ..
- Hecht J, Siegenthaler J, Patterson K, Pleasure S. Primary cellular meningeal defects cause neocortical dysplasia and dyslamination. Ann Neurol. 2010;68:454-64 pubmed publisher..Specific changes in basement membrane composition may contribute to subsequent breakdown. Our study raises the possibility that primary meningeal defects may cortical dysplasia in some cases. ..
- Iivanainen A, Kortesmaa J, Sahlberg C, Morita T, Bergmann U, Thesleff I, et al. Primary structure, developmental expression, and immunolocalization of the murine laminin alpha4 chain. J Biol Chem. 1997;272:27862-8 pubmed..Immunohistologic staining with affinity-purified IgG localized the laminin alpha4 chain primarily to lung septa, heart, and skeletal muscle, capillaries, and perineurium. ..
- Kenne E, Soehnlein O, Genove G, Rotzius P, Eriksson E, Lindbom L. Immune cell recruitment to inflammatory loci is impaired in mice deficient in basement membrane protein laminin alpha4. J Leukoc Biol. 2010;88:523-8 pubmed publisher..Collectively, our data suggest a reduced ability of immune cells to penetrate the vessel wall in mice deficient in laminin alpha4. ..
- Chand K, Lee K, Lavidis N, Noakes P. Loss of laminin-?4 results in pre- and postsynaptic modifications at the neuromuscular junction. FASEB J. 2017;31:1323-1336 pubmed publisher..Chand, K. K., Lee, K. M., Lavidis, N. A., Noakes, P. G. Loss of laminin-?4 results in pre- and postsynaptic modifications at the neuromuscular junction. ..
- Bolcato Bellemin A, Lefebvre O, Arnold C, Sorokin L, Miner J, Kedinger M, et al. Laminin alpha5 chain is required for intestinal smooth muscle development. Dev Biol. 2003;260:376-90 pubmed
- Wallquist W, Plantman S, Thams S, Thyboll J, Kortesmaa J, Lannergren J, et al. Impeded interaction between Schwann cells and axons in the absence of laminin alpha4. J Neurosci. 2005;25:3692-700 pubmed..Thus, laminin-2 and laminin-8 have different critical functions in peripheral nerves, mediated by different integrin receptors. ..
- Kim I, Ramakrishna S, Gusarova G, Yoder H, Costa R, Kalinichenko V. The forkhead box m1 transcription factor is essential for embryonic development of pulmonary vasculature. J Biol Chem. 2005;280:22278-86 pubmed..17 (ADAM-17), vascular endothelial growth factor receptors, Polo-like kinase 1, Aurora B kinase, laminin alpha4 (Lama4), and the Forkhead Box f1 transcription factor...
- Wang J, Hoshijima M, Lam J, Zhou Z, Jokiel A, Dalton N, et al. Cardiomyopathy associated with microcirculation dysfunction in laminin alpha4 chain-deficient mice. J Biol Chem. 2006;281:213-20 pubmed..Moreover, cardiomyocytes isolated from Lama4-/- mutant hearts maintained their contractility in vitro...