Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

Figure 2

Ultrastructural elements (a–d) of the basement membrane (BM) zone in skin, ultrastructural alignments (b–d), and prototypes of laminin isoforms (e). The cartoon (a) depicts the anchoring structures between epidermis (E) and dermis (D) corresponding to the ultrastructure of the collagen-epidermal interface (b) of a 3D coculture of keratinocytes with fibroblasts, resembling skin. Immune-EM demonstrates the coalignment of collagen IV with the lamina densa (c) and colocalization of integrin α6β4 with laminin-332 ((d); small/large gold particles). Three laminin subtypes, being also present in adult skin, are shown in (e), represented by the main adult BM-type laminin-511, the vascular laminin-411, and laminin-332 found in anchoring filaments. Like laminin-511, most isoforms carry three N-terminal self-assembly sites (∗) required for two-dimensional polymerization. Some other like laminin-411 have only two, and, as an exception, laminin-332 has only one of those “sticky” sites. Common to all are the C-terminal cell-binding sites (∗∗); large arrows point to the γ1 nidogen-binding domain. Further typical for laminin-332 is extensive proteolytic processing with the major cleavage sites (marked by small arrows) at the short arm of the γ2 and the C-terminus of the α3 chain (see also: [78, 125]). (Slightly modified from [18] [with kind permission from Springer Science + Business Media]).