title: The juxtamembrane region of synaptotagmin 1 interacts with dynamin 1 and regulates vesicle fission during compensatory endocytosis in endocrine cells.
abstract: Synaptotagmin 1 (Syt1) is a synaptic vesicle protein that is important for the kinetics of both exocytosis and endocytosis, and is thus a candidate molecule to link these two processes. Although the tandem Ca(2+)-binding C2 domains of Syt1 have important roles in exocytosis and endocytosis, the function of the conserved juxtamembrane (jxm) linker region has yet to be determined. We now demonstrate that the jxm region of Syt1 interacts directly with the pleckstrin homology (PH) domain of the endocytic protein dynamin 1. By using cell-attached capacitance recordings with millisecond time resolution to monitor clathrin-mediated endocytosis of single vesicles in neuroendocrine chromaffin cells, we find that loss of this interaction prolongs the lifetime of the fission pore leading to defects in the dynamics of vesicle fission. These results indicate a previously undescribed interaction between two major regulatory proteins in the secretory vesicle cycle and that this interaction regulates endocytosis.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: McAdam
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Varga
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Zhongjiao
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Fiona B
authors.initials: FB
authors.lastname: Young
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Blandford
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Peter S
authors.initials: PS
authors.lastname: McPherson
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Liang-Wei
authors.initials: LW
authors.lastname: Gong
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada wayne.sossin@mcgill.ca.
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Sossin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D034284:Dynamin I / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D050863:Synaptotagmin I / Q000502:physiology*
chemical_list: D002966:Clathrin; D050863:Synaptotagmin I; D034284:Dynamin I; D002118:Calcium
keywords: Chromaffin cells; Compensatory endocytosis; Dynamin; Synaptotagmin; Syt1