The shed ectodomain of type XIII collagen affects cell behaviour in a matrix-dependent manner.
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.
Väisänen
Marja-Riitta
MR
Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
Väisänen
Timo
T
Pihlajaniemi
Taina
T
D000954:Antigens, Surface / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D024181:Collagen Type XIII / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000196:embryology / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000502:physiology*; D045683:Furin / Q000172:deficiency; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D043484:Proprotein Convertases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012867:Skin / Q000166:cytology; D013997:Time Factors
D000954:Antigens, Surface; D024181:Collagen Type XIII; D008565:Membrane Proteins; D011480:Protease Inhibitors; D043484:Proprotein Convertases; D045683:Furin