title: Synaptotagmin-1- and Synaptotagmin-7-Dependent Fusion Mechanisms Target Synaptic Vesicles to Kinetically Distinct Endocytic Pathways.
abstract: Synaptic vesicle recycling is essential for maintaining normal synaptic function. The coupling of exocytosis and endocytosis is assumed to be Ca2+dependent, but the exact role of Ca2+and its key effector synaptotagmin-1 (syt1) in regulation of endocytosis is poorly understood. Here, we probed the role of syt1 in single- as well as multi-vesicle endocytic events using high-resolution optical recordings. Our experiments showed that the slowed endocytosis phenotype previously reported after syt1 loss of function can also be triggered by other manipulations that promote asynchronous release such as Sr2+substitution and complexin loss of function. The link between asynchronous release and slowed endocytosis was due to selective targeting of fused synaptic vesicles toward slow retrieval by the asynchronous release Ca2+sensor synaptotagmin-7. In contrast, after single synaptic vesicle fusion, syt1 acted as an essential determinant of synaptic vesicle endocytosis time course by delaying the kinetics of vesicle retrieval in response to increasing Ca2+levels.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
authors.forename: Ying C
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
authors.forename: Natali L
authors.initials: NL
authors.lastname: Chanaday
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA. Electronic address: ege.kavalali@utsouthwestern.edu.
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
mesh_terms: D000200:Action Potentials; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology; D008561:Membrane Fusion / Q000235:genetics; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D050863:Synaptotagmin I / Q000235:genetics*; D050857:Synaptotagmins / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C095992:complexin I; C095993:complexin II; D050857:Synaptotagmins; D002118:Calcium
keywords: asynchronous release; calcium regulation of endocytosis; complexin; endocytosis; single-vesicle imaging; synaptic vesicle endocytosis; synaptic vesicle recycling; synaptotagmin-1; synaptotagmin-7; synchronous release