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Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5210-4. Epub 2005 Mar 25.

Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis.

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  • 1Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.


Synaptotagmins (syts) are a family of membrane proteins present on a variety of intracellular organelles. In vertebrates, 16 isoforms of syt have been identified. The most abundant isoform, syt I, appears to function as a Ca2+ sensor that triggers the rapid exocytosis of synaptic vesicles from neurons. The functions of the remaining syt isoforms are less well understood. The cytoplasmic domain of syt I binds membranes in response to Ca2+, and this interaction has been proposed to play a key role in secretion. Here, we tested the Ca(2+)-triggered membrane-binding activity of the cytoplasmic domains of syts I-XII; eight isoforms tightly bound to liposomes that contained phosphatidylserine as a function of the concentration of Ca2+. We then compared the disassembly kinetics of Ca2+.syt.membrane complexes upon rapid mixing with excess Ca2+ chelator and found that syts can be classified into three distinct kinetic groups. syts I, II, and III constitute the fast group; syts V, VI, IX, and X make up the medium group; and syt VII exhibits the slowest kinetics of disassembly. Thus, isoforms of syt, which have much slower disassembly kinetics than does syt I, might function as Ca2+ sensors for asynchronous release, which occurs after Ca2+ domains have collapsed. We also compared the temperature dependence of Ca2+.syt.membrane assembly and disassembly reactions by using squid and rat syt I. These results indicate that syts have diverged to release Ca2+ and membranes with distinct kinetics.

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