Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells.
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.
Lynch
Kara L
KL
Department of Biochemistry, 433 Babcock Drive, University of Wisconsin, Madison, WI 53706, USA.
Martin
Thomas F J
TF
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D007150:Immunohistochemistry; D007700:Kinetics; D008969:Molecular Sequence Data; D016716:PC12 Cells; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D050863:Synaptotagmin I / Q000737:chemistry / Q000378:metabolism*; D050857:Synaptotagmins / Q000737:chemistry / Q000378:metabolism*
D050863:Synaptotagmin I; D050857:Synaptotagmins; D002118:Calcium