Väisänen Marja-Riitta, Väisänen Timo, Pihlajaniemi Taina
Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
Biochem J. 2004 Jun 15;380(Pt 3):685-93. doi: 10.1042/BJ20031974.
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.
跨膜型 XIII 胶原蛋白存在于细胞和组织的黏附结构中，因此与细胞黏附及黏附依赖性细胞功能有关。这种胶原蛋白也以可溶性蛋白的形式存在于细胞周基质中，因为其胞外结构域通过蛋白水解切割从质膜上释放出来。用各种蛋白酶抑制剂进行分析，证实了前蛋白转化酶弗林家族是负责胞外结构域脱落的蛋白酶组，其在胞外结构域茎部符合前蛋白转化酶共有序列的位点进行切割。反式高尔基体网络和质膜均被用作切割位点。哺乳动物细胞采用多种细胞内机制来调节胞外结构域的脱落，所有这些机制都导致类似的切割事件。还发现细胞从下层基质脱离会增强这种切割。释放的胞外结构域使细胞周环境对细胞黏附、迁移和增殖的支持作用减弱，这在玻连蛋白基质上尤为明显。因此， XIII 型胶原蛋白胞外结构域的脱落导致形成一种可溶性的生物活性分子，该分子最终以相互作用且依赖基质的方式调节细胞行为。膜结合型和可溶性变体的双重存在拓宽了我们对 XIII 型胶原蛋白的生物学理解。
