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.