Laminin Polymerization and Inherited Disease: Lessons From Genetics

Shaw, Liam, Sugden, Conor J ORCID: 0000-0002-9543-1676 and Hamill, Kevin J ORCID: 0000-0002-7852-1944 (2021) Laminin Polymerization and Inherited Disease: Lessons From Genetics. FRONTIERS IN GENETICS, 12. 707087-.

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Official URL: http://dx.doi.org/10.3389/fgene.2021.707087

Abstract

The laminins (LM) are a family of basement membranes glycoproteins with essential structural roles in supporting epithelia, endothelia, nerves and muscle adhesion, and signaling roles in regulating cell migration, proliferation, stem cell maintenance and differentiation. Laminins are obligate heterotrimers comprised of α, β and γ chains that assemble intracellularly. However, extracellularly these heterotrimers then assemble into higher-order networks <i>via</i> interaction between their laminin N-terminal (LN) domains. <i>In vitro</i> protein studies have identified assembly kinetics and the structural motifs involved in binding of adjacent LN domains. The physiological importance of these interactions has been identified through the study of pathogenic point mutations in LN domains that lead to syndromic disorders presenting with phenotypes dependent on which laminin gene is mutated. Genotype-phenotype comparison between knockout and LN domain missense mutations of the same laminin allows inferences to be drawn about the roles of laminin network assembly in terms of tissue function. In this review, we will discuss these comparisons in terms of laminin disorders, and the therapeutic options that understanding these processes have allowed. We will also discuss recent findings of non-laminin mediators of laminin network assembly and their implications in terms of basement membrane structure and function.

Item Type:	Article
Uncontrolled Keywords:	laminin, netrin, Pierson syndrome, MDC1A, basement membrane, junctional epidermolysis bullosa
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	17 Sep 2021 15:10
Last Modified:	18 Jan 2023 21:28
DOI:	10.3389/fgene.2021.707087
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3137403