Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation.
Palmitoylation regulates diverse aspects of neuronal protein trafficking and function. Here a global characterization of rat neural palmitoyl-proteomes identifies most of the known neural palmitoyl proteins-68 in total, plus more than 200 new palmitoyl-protein candidates, with further testing confirming palmitoylation for 21 of these candidates. The new palmitoyl proteins include neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins, as well as SNAREs and other vesicular trafficking proteins. Of particular interest is the finding of palmitoylation for a brain-specific Cdc42 splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs from the canonical, prenylated form (Cdc42-prenyl), both with regard to localization and function: Cdc42-palm concentrates in dendritic spines and has a special role in inducing these post-synaptic structures. Furthermore, assessing palmitoylation dynamics in drug-induced activity models identifies rapidly induced changes for Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that palmitoylation may participate broadly in the activity-driven changes that shape synapse morphology and function.
Kang
Rujun
R
Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada. rkang@interchange.ubc.ca
Wan
Junmei
J
Arstikaitis
Pamela
P
Takahashi
Hideto
H
Huang
Kun
K
Bailey
Aaron O
AO
Thompson
James X
JX
Roth
Amy F
AF
Drisdel
Renaldo C
RC
Mastro
Ryan
R
Green
William N
WN
Yates
John R
JR
Davis
Nicholas G
NG
El-Husseini
Alaa
A
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D003712:Dendrites / Q000378:metabolism; D054878:Lipoylation; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D020543:Proteome; D020764:cdc42 GTP-Binding Protein