Laminin isoforms in development and disease.
The members of the laminin family of heterotrimers are major constituents of all basement membranes, sheet-like extracellular structures, present in almost all organs. The laminins bind to cell surface receptors and thereby tightly connect the basement membrane to the adjacent cell layer. This provides for the specific basement membrane functions to stabilize cellular structures, to serve as effective physical barriers, and furthermore, to govern cell fate by inducing intracellular signalling cascades. Many different types of diseases involve basement membranes and laminins. Metastasizing solid tumors must pass through basement membranes to reach the vascular system, and various microbes and viruses enter the cells through direct interaction with laminins. Furthermore, whereas mutations in one specific laminin chain lead to a muscular disorder, mutations of other laminin chains cause skin blistering and kidney defects, respectively. This review summarizes recent progress concerning the molecular mechanisms of laminins in development and disease. The current knowledge may lead to clinical treatment of lamininopathies and may include stem-cell approaches as well as gene therapy.
Schéele
Susanne
S
Section for Cell and Matrix Biology, BMC B12, Department of Experimental Medical Science, Lund University, Sölvegatan 19, 22184, Lund, Sweden. susanne.scheele@med.lu.se
Nyström
Alexander
A
Durbeej
Madeleine
M
Talts
Jan F
JF
Ekblom
Marja
M
Ekblom
Peter
P
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D049030:Dystroglycans / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D016023:Integrins; D007797:Laminin; D020033:Protein Isoforms; D049030:Dystroglycans