The shed ectodomain of type XIII collagen affects cell behaviour in a matrix-dependent manner

Abstract

Transmembrane type XIII collagen resides in adhesive structures of cells and tissues, and has therefore been implicated in cell adhesion and in adhesion-dependent cell functions. This collagen also exists as a soluble protein in the pericellular matrix, as the ectodomain is released from the plasma membrane by proteolytic cleavage. Analysis with various protease inhibitors led to confirmation of the furin family of proprotein convertases as the protease group responsible for the shedding of the ectodomain, cleaving at a site conforming to the consensus sequence for the proprotein convertases at the stem of the ectodomain. Both the trans -Golgi network and the plasma membrane were used as cleavage locations. Mammalian cells employed various intracellular mechanisms to modulate shedding of the ectodomain, all resulting in a similar cleavage event. Cell detachment from the underlying substratum was also found to augment the excision. The released ectodomain rendered the pericellular surroundings less supportive of cell adhesion, migration and proliferation, as seen specifically on a vitronectin substratum. Type XIII collagen ectodomain shedding thus resulted in the formation of a soluble, biologically active molecule, which eventually modulated cell behaviour in a reciprocal and substratum-specific manner. The dual existence of membrane-bound and soluble variants widens our biological understanding of type XIII collagen.

Shedding of Collagen XXIII Is Mediated by Furin and Depends on the Plasma Membrane Microenvironment

“…To get an idea whether other PCs are able to compensate for furin activity, LoVo cells, which are known to lack furin but still contain active PACE4 and PC7 (4,25,26), were employed. Upon transfection with full-length ␣1(XXIII) cDNA, they showed strongly reduced shedding of collagen XXIII compared with other transfected cell lines (supplemental Fig.…”

“…Whereas collagen XVII is more distantly related, types XIII, XVII, XXIII, and XXV all exist in two forms: a transmembrane form and a shed ectodomain form. Whereas collagen XVII is shed from the surface by TACE (tumor necrosis factor-␣-converting enzyme), a member of the ADAM (a disintegrin and metalloproteinase) family (2), mutation analysis of collagens XIII and XXV demonstrated that the protease furin produces the shed forms (3,4). Initial cell culture studies suggested an involvement of furin either directly or indirectly in the cleavage of collagen XXIII as well (5).…”

Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site

“…They are also implicated in the ectodomain shedding of some substrates such as type XIII collagen [43]. The involvement of proprotein convertases in ectodomain shedding could be either through direct cleavage of the substrate, or indirect activation of ADAMs and MMPs.…”

Cleavage and Oligomerization of Gliomedin, a Transmembrane Collagen Required for Node of Ranvier Formation

“…Presumably, ectodomain in cell extracts is derived from gliomedin molecules still anchored in the cell membrane because one or two of the three chains remains uncleaved by furin. Pulse-chase experiments on cells expressing membrane-bound gliomedin revealed rapid shedding of the protein from cell surfaces as shown for collagens XVII and XIII (3,41).…”