Assembly. structure and function of basement membranes
Basement membranes are specialized cell-associated extracellular
matrices whose molecular architectures are created through specific binding
interactions of unique monomers. These matrices have support. perm-selective
and cell regulatory functions. Both structure and function are altered in
a number of diseases such as diabetes mellitus. Alports Syndrome. epidermolysis
bullosa and some forms of congenital muscular dystrophy. The monomeric untis
of basement membranes are. in themselves. large multi-domain glycoproteins
and proteoglycans. each with several functions. Laminin and type IV collagen. for example. form polymeric networks as well as selectively bind and activate
a number of different cellular receptors. Our fundamental research goals
are to understand structure/function relationships in basement membranes
at a molecular level of resolution. in particular: (a) the mechanisms of
self-assembly and its regulation. the resulting molecular architectures. and how supramolecular organization contributes to function. (b) how structure
and function become altered in diabetes. (c) the ole. and structural basis. of basement membranes. and their supramolecular assemblies. in the transmission
of information to cells. These signals are mediated by beta-1. beta-3. and
beta-4 class integrins. dystroglycan. and other cell-surface proteoglycans. and (d) the differential structural and cell-interactive information carried
by the genetic variants of laminin and type IV collagen.
|
