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Published July 2004 | public
Journal Article

Spinophilin is phosphorylated by Ca^(2+)/calmodulin-dependent protein kinase II resulting in regulation of its binding to F-actin

Abstract

Spinophilin is a protein phosphatase-1- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology. We have recently shown that the interaction of spinophilin with the actin cytoskeleton depends upon phosphorylation by protein kinase A. We have now found that spinophilin is phosphorylated by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) in neurons. Ca^(2+)/calmodulin-dependent protein kinase II, located within the post-synaptic density of dendritic spines, is known to play a role in synaptic plasticity and is ideally positioned to regulate spinophilin. Using tryptic phosphopeptide mapping, site-directed mutagenesis and microsequencing analysis, we identified two sites of CaMKII phosphorylation (Ser-100 and Ser-116) within the actin-binding domain of spinophilin. Phosphorylation by CaMKII reduced the affinity of spinophilin for F-actin. In neurons, phosphorylation at Ser-100 by CaMKII was Ca^(2+) dependent and was associated with an enrichment of spinophilin in the synaptic plasma membrane fraction. These results indicate that spinophilin is phosphorylated by multiple kinases in vivo and that differential phosphorylation may target spinophilin to specific locations within dendritic spines.

Additional Information

© 2004 International Society for Neurochemistry Received January 21, 2004; revised manuscript received March 3, 2004; accepted March 3, 2004. This work was supported by U.S.P.H.S. grants MH40899 and DA10044 (to ACN, GLS and PG), fellowship DRG-1451 of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation (LCH-W), The National Alliance for Research on Schizophrenia and Depression (to SDG and PBA) and The Michael Stern Parkinson's Research Foundation.

Additional details

Created:
August 22, 2023
Modified:
October 23, 2023