Type IV collagen

Type IV collagen, the best-characterized example of a coUagen with discontinuous triple helices, is an important component of basement membranes, where it forms a mesh-hke network. 

Basal laminas are specialized areas of the ECM that surround epithelial and some other cells (eg, muscle cells) here we discuss only the laminas found in the renal glomerulus. In that strucmre, the basal lamina is contributed by two separate sheets of cells (one endothelial and one epithelial), each disposed on opposite sides of the lamina these three layers make up the glomerular membrane. The primary components of the basal lamina are three proteins—laminin, entactin, and type IV collagen—and the GAG heparin or heparan sulfate. These components are synthesized by the underlying cells. 

Certain proteoglycans (eg, heparan sulfate) are associated with the plasma membrane of cells, with their core proteins acmally spanning that membrane. In it they may act as receptors and may also participate in the mediation of cell growth and cell-cell communication. The attachment of cells to their substramm in cul-mre is mediated at least in part by heparan sulfate. This proteoglycan is also found in the basement membrane of the kidney along with type IV collagen and laminin... 

The lens is an avascular transparent tissue enveloped in the lens capsule, a basement membrane composed of type IV collagen (Harding and Crabbe, 1984). The single layer of epithelial cells under the anterior portion of the capsule divide throughout life, accumulate crystaUin... 

Expression of matrix metalloproteinases (MMPs) and their inhibitors is an important function of the RPE, particularly with respect to the maintenance of appropriate permeability of the Bruch s membrane (Ahir et al., 2002). This function can be tested in vitro (Marin-Castano et al., 2006). For example, it has been shown that the expression of MMP-2, TIPM-2s (tissue inhibitor of MMP-2), and type IV collagen by cultured ARPE-19 cells is affected by repetitive exposures to nonlethal oxidant injury with hydroquinone (Marin-Castano et al., 2006). Oxidative stress decreases MMP-2 activity and increases collagen type IV accumulation. 

Brown Norway rat HgCl2 AU-salts D-Penicillamine Nevirapine HCB IC-glomerulonephritis Skin pathology, dermatitis Polyclonal IgE AutoAb (Type IV-collagen, ANA, 1 anti-ACh, thyroglobulin) Systemic inflamatory response with autoimmune symptoms... 

LH3 null mice are embryonic lethal at E9.5-14.5, show fragmentation of basement membrane and possibly some type IV collagen abnormalities... 

The type IV collagen molecule is comprised of the N-terminal collagenous 7S domain, which has a sedimentation coefficient of the central major collagenous domain with more than 20 interruptions... 

Type IV collagen subtype [ctl(IV)]2Q 2(IV) from bovine lens capsule forms a fine meshwork structure containing many branches with about 20 nm between the branching points. There are three types of supramolecular assembly of type IV collagen molecules dimer formation (with six polypeptide chains) at the C-terminal NCI domain, the association of four molecules (12 chains) in a 30 nm tetramer formation at the N-terminal 7S domain, and lateral interaction at the collagenous domain (Figure 5(a)). ° ... 

Figure 5 (a) Supramolecular assembly of type IV collagen molecules (1) a dimer formation at the C-terminal NC1 domain, (2) the association of four molecules at the N-terminal 7S domain, and (3) lateral interaction at the collagenous domain. 

The NCI domain of type VII collagen binds to the /33 chain of laminin, " laminin-5 a3(33 2), and type IV collagen. The triple helical domain of type VII collagen functions to promote the migration of human keratinocytes. °... 

Figure 20 Ribbon representationsof structures of the type IV collagen NCI trimer (PDB accession number 1M3D) (a) down the pseudo-three-fold axis and hexamer (b) down the two-fold NCS axis. The figure was generated using the UCSF Chimera package.

Despite the requirement ofNC domains for correct oligomerization of the collagen triple helix, the NC domain structures are divergent among all collagens. The structure of the NCI domain of type IV collagen " is... 

Tropocollagen molecules are firmly linked together, particularly at their ends, by covalent networks of altered lysine side chains. The number of these links increases with age. Type IV collagens form networks with a defined mesh size. The size-selective filtering effect of the basal membranes in the renal glomeruli is based on this type of structure (see p. 322). 

---