SPIN90 phosphorylation modulates spine structure and synaptic function.
The correct rearrangement of postsynaptic components in dendritic spines is important for driving changes of spine structure and synaptic function. SPIN90 plays an essential role in many cellular processes including actin polymerization, endocytosis, growth cone formation and dendritic spine morphogenesis. Here, we demonstrate that SPIN90, which is a binding partner of PSD95 and Shank in spines, is targeted to synapses and leads to enhanced synaptic activity in neurons. We show, using in vitro and in vivo kinase assays, that SPIN90 is tyrosine phosphorylated by Src kinase. SPIN90 that was tyrosine-phosphorylated by Src was targeted to dendritic spines in cultured hippocampal neurons. Moreover, a SPIN90 phospho-deficient mutant was unable to accumulate at dendritic spines whereas SPIN90 WT and a phospho-mimicking mutant were localized at spines and bound PSD95 and Shank with increased efficiency. Consistent with these findings, hippocampal neurons that overexpressed SPIN90 WT or a phospho-mimicking mutant had enlarged spine heads, leading to enhanced postsynaptic function in terms of both amplitude and frequency. Together, our findings show that SPIN90 modulates synaptic activity in neurons as a result of its phosphorylation.
Bio Imaging and Cell Dynamics Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
In Ha
IH
Cho
Dae Hwan
DH
Kim
Min-Jung
MJ
Lee
Jeomil
J
Bae
Kun Ho
KH
Lee
Woo Keun
WK
Song
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation; D009124:Muscle Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D013131:Spine / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; C486062:NCKIPSD protein, human; D009419:Nerve Tissue Proteins; C542056:SPIN90 protein, mouse