Presynaptic trafficking of synaptotagmin I is regulated by protein palmitoylation.
Protein palmitoylation plays a critical role in sorting and targeting of several proteins to pre- and postsynaptic sites. In this study, we have analyzed the role of palmitoylation in trafficking of synaptotagmin I and its modulation by synaptic activity. We found that palmitoylation of N-terminal cysteines contributed to sorting of synaptotagmin I to an intracellular vesicular compartment at the presynaptic terminal. Presynaptic targeting is a unique feature of N-terminal sequences of synaptotagmin I because the palmitoylated N terminus of synaptotagmin VII failed to localize to presynaptic sites. We also found that palmitate was stably associated with both synaptotagmin I and SNAP-25 and that rapid neuronal depolarization did not affect palmitate turnover on these proteins. However, long-term treatment with drugs that either block synaptic activity or disrupt SNARE complex assembly modulated palmitoylation and accumulation of synaptotagmin I at presynaptic sites. We conclude that palmitoylation is involved in trafficking of specific elements involved in transmitter release and that distinct mechanisms regulate addition and removal of palmitate on select neuronal proteins.
Kang
Rujun
R
Department of Psychiatry, Centre for Complex Disorders, University of British Columbia, Vancouver, British Columbia, Canada.
Swayze
Richard
R
Lise
Marie France
MF
Gerrow
Kimberly
K
Mullard
Asher
A
Honer
William G
WG
El-Husseini
Alaa
A
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates; C494208:SNAP25 protein, human; C494310:SYT1 protein, human; C494302:SYT7 protein, human; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C494304:Syt7 protein, rat; D050857:Synaptotagmins