Synaptotagmin 1 is the Ca2+ Sensor for the Endocytic Kinetics of Clathrin-Mediated Endocytosis
thesisposted on 28.10.2014 by Kelly T. Varga
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
After neurotransmitter release via exocytosis, synaptic vesicles are locally retrieved, re-filled and made readily available for the next round of release at the synapse (Heuser & Reese, 1973; Miller & Heuser, 1984). While the role of Ca2+ has long been established to be essential in triggering exocytosis (Neher and Sakaba, 2008), recent studies indicate a direct role of Ca2+ in endocytosis as well (Wu et al., 2007). Along this line, synaptotagmin 1 (Syt1), a synaptic vesicular protein, , is well established as the Ca2+ sensor to trigger vesicle exocytosis (Chapman, 2008) and recent evidence indicates that this protein may also play Ca2+ dependent roles in endocytosis (Nicholson-Tomishima & Ryan, 2004, please recite more papers for this). However, the molecular details for the role of Ca2+ and Syt1 in vesicle endocytosis remains poorly understood. In the present study, by taking advantages of millisecond time resolution of cell-attached capacitance measurements to monitor clathrin-mediated endocytosis (CME), the classic retrieval pathway at synaptic terminals (Murthy & De Camilli, 2003; Granseth et al., 2006), I demonstrate for the first time that: 1) the dynamics of vesicle fission during CME is both Ca2+- and Syt1- dependent; 2) Syt1 may serve as the biochemical Ca2+sensor of CME and 3) that the interaction between Syt1 and phosphatidylserine, a putative Ca2+ dependent interaction, may be critical for the Ca2+ sensing role of Syt1 in CME kinetics