Unexpected Ca2+-binding properties of synaptotagmin 9.

Ok-Ho Shin, Anton Maximov, Byung Kook Lim, Josep Rizo, Thomas C Südhof

Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, Dallas, TX 75390-9111, USA.

Proceedings of the National Academy of Sciences of the United States of America 2004 Feb 24

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Synaptotagmin 1 (Syt 1) functions as an essential Ca2+ sensor for the fast but not slow component of Ca2+-triggered exocytosis. One hypothesis to account for this selective function, based on the close homology of Syt 1 with synaptotagmin 9 (Syt 9), is that these Syts are redundant for the slow but not the fast component of release. We now show, however, that Syt 9 has unique properties that set it apart from Syt 1. Different from Syt 1, endogenous Syt 9 does not associate Ca2+ dependently or independently with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein complexes, and the Syt 9 C2B domain does not form Ca2+/phospholipid complexes, whereas such complexes are essential for Syt 1 function. Nevertheless, the C2A domain of Syt 9 functions as a Ca2+-binding module, suggesting that Syts 1 and 9 are Ca2+ sensors with similar Ca2+-binding sequences but distinct properties that indicate nonoverlapping functions.

Citation

Ok-Ho Shin, Anton Maximov, Byung Kook Lim, Josep Rizo, Thomas C Südhof. Unexpected Ca2+-binding properties of synaptotagmin 9. Proceedings of the National Academy of Sciences of the United States of America. 2004 Feb 24;101(8):2554-9