Unexpected Ca2+-binding properties of synaptotagmin 9.
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.
Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, Dallas, TX 75390-9111, USA.
Ok-Ho
OH
Shin
Anton
A
Maximov
Byung Kook
BK
Lim
Josep
J
Rizo
Thomas C
TC
Südhof
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005089:Exocytosis; D013006:Growth Hormone / Q000378:metabolism; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C483193:Syt9 protein, rat; D050857:Synaptotagmins; D013006:Growth Hormone; D002118:Calcium