Lynch Kara L, Martin Thomas F J
Department of Biochemistry, 433 Babcock Drive, University of Wisconsin, Madison, WI 53706, USA.
J Cell Sci. 2007 Feb 15;120(Pt 4):617-27. doi: 10.1242/jcs.03375. Epub 2007 Jan 30.
Synaptotagmin I is considered to be a Ca2+ sensor for fast vesicle exocytosis. Because Ca2+-dependent vesicle exocytosis persists in synaptotagmin I mutants, there must be additional Ca2+ sensors. Multiple synaptotagmin isoforms co-reside on vesicles, which suggests that other isoforms complement synaptotagmin I function. We found that full downregulation of synaptotagmins I and IX, which co-reside on vesicles in PC12 cells, completely abolished Ca2+-dependent vesicle exocytosis. By contrast, Ca2+-dependent exocytosis persisted in cells expressing only synaptotagmin I or only synaptotagmin IX, which indicated a redundancy in function for these isoforms. Although either isoform was sufficient to confer Ca2+ regulation on vesicle exocytosis, synaptotagmins I and IX conferred faster and slower release rates, respectively, indicating that individual isoforms impart distinct kinetic properties to vesicle exocytosis. The downregulation of synaptotagmin I but not synaptotagmin IX impaired compensatory vesicle endocytosis, which revealed a lack of isoform redundancy and functional specialization of synaptotagmin I for endocytic retrieval.
突触结合蛋白I被认为是快速囊泡胞吐作用的钙离子传感器。由于钙离子依赖性囊泡胞吐作用在突触结合蛋白I突变体中持续存在，因此必定存在其他钙离子传感器。多种突触结合蛋白亚型共同存在于囊泡上，这表明其他亚型可补充突触结合蛋白I的功能。我们发现，在PC12细胞中共同存在于囊泡上的突触结合蛋白I和IX完全下调时，会完全消除钙离子依赖性囊泡胞吐作用。相比之下，钙离子依赖性胞吐作用在仅表达突触结合蛋白I或仅表达突触结合蛋白IX的细胞中持续存在，这表明这些亚型在功能上具有冗余性。尽管任何一种亚型都足以赋予囊泡胞吐作用钙离子调节能力，但突触结合蛋白I和IX分别赋予更快和更慢的释放速率，这表明单个亚型赋予囊泡胞吐作用不同的动力学特性。突触结合蛋白I而非突触结合蛋白IX的下调会损害代偿性囊泡内吞作用，这揭示了突触结合蛋白I在内吞回收方面缺乏亚型冗余性和功能特异性。
