Function
Laminins (LAM) are a family of glycoproteins that provide the integral part of the structural scaffolding of basement membranes in almost every animal tissue. Laminins are heterotrimers containing α-, β- and γ-subunits[1]. Laminins are essential for early embryonic development and organogenesis and have crucial functions in tissues like muscles, lung, skin, kidney and nerve[2]. Several members of the integrin family serve as laminin receptors on a variety of cell types[3].
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Disease
Relevance
Serum concentration of laminin is increased in patients with inflammatory bowel disease hence can be used as a marker for sustained inflammation[4]. Laminin was found to have an anti-amyloidogenic effect and γmay be of therapeutic value in Alzheimer Disease[5]. Laminin-111 was found to be a highly therapeutic agent in mice with Duchenne muscular dystrophy[6].
Structural highlights
The interaction os laminin with integrin β1 metlion-dependent adhesion site is via the LAM γ chain tail. The critical LAM residue for binding integrin is a Glu residue in chain γ-1[7].
- ↑ Colognato H, Yurchenco PD. Form and function: the laminin family of heterotrimers. Dev Dyn. 2000 Jun;218(2):213-34. doi:, 10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R. PMID:10842354 doi:<213::AID-DVDY1>3.0.CO;2-R https://dx.doi.org/10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R
- ↑ Durbeej M. Laminins. Cell Tissue Res. 2010 Jan;339(1):259-68. doi: 10.1007/s00441-009-0838-2. Epub, 2009 Aug 20. PMID:19693542 doi:https://dx.doi.org/10.1007/s00441-009-0838-2
- ↑ Belkin AM, Stepp MA. Integrins as receptors for laminins. Microsc Res Tech. 2000 Nov 1;51(3):280-301. doi:, 10.1002/1097-0029(20001101)51:3<280::AID-JEMT7>3.0.CO;2-O. PMID:11054877 doi:<280::AID-JEMT7>3.0.CO;2-O https://dx.doi.org/10.1002/1097-0029(20001101)51:3<280::AID-JEMT7>3.0.CO;2-O
- ↑ Koutroubakis IE, Petinaki E, Dimoulios P, Vardas E, Roussomoustakaki M, Maniatis AN, Kouroumalis EA. Serum laminin and collagen IV in inflammatory bowel disease. J Clin Pathol. 2003 Nov;56(11):817-20. doi: 10.1136/jcp.56.11.817. PMID:14600124 doi:https://dx.doi.org/10.1136/jcp.56.11.817
- ↑ Morgan C, Inestrosa NC. Interactions of laminin with the amyloid beta peptide. Implications for Alzheimer's disease. Braz J Med Biol Res. 2001 May;34(5):597-601. doi:, 10.1590/s0100-879x2001000500006. PMID:11323745 doi:https://dx.doi.org/10.1590/s0100-879x2001000500006
- ↑ Rooney JE, Gurpur PB, Burkin DJ. Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7991-6. doi:, 10.1073/pnas.0811599106. Epub 2009 Apr 28. PMID:19416897 doi:https://dx.doi.org/10.1073/pnas.0811599106
- ↑ Takizawa M, Arimori T, Taniguchi Y, Kitago Y, Yamashita E, Takagi J, Sekiguchi K. Mechanistic basis for the recognition of laminin-511 by alpha6beta1 integrin. Sci Adv. 2017 Sep 1;3(9):e1701497. doi: 10.1126/sciadv.1701497. eCollection 2017 , Sep. PMID:28879238 doi:https://dx.doi.org/10.1126/sciadv.1701497