Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus

The consequences of the rapid 3-phosphorylation of inositol 1,4,5-trisphosp hate (IP3) to produce inositol 1,3,4,5-tetrakisphosphate (IP4) via the acti on of IP3 3-kinases involve the control of calcium signals. Using green flu orescent protein constructs of full-length and truncated IP3 3-kinase isofo rm A expressed in HeLa cells, COS-7 cells, and primary neuronal cultures, w e have defined a novel N-terminal 66-amino acid F-actin-binding region that localizes the kinase to dendritic spines. The region is necessary and suff icient for binding F-actin and consists of a proline-rich stretch followed by a predicted alpha -helix. We also localized endogenous IP3 3-kinase A to the dendritic spines of pyramidal neurons in primary hippocampal cultures, where it is co-localized postsynaptically with calcium/calmodulin-dependen t protein kinase II. Our experiments suggest a link between inositol phosph ate metabolism, calcium signaling, and the actin cytoskeleton in dendritic spines. The phosphorylation of IP3 in dendritic spines to produce IP4 is li kely to be important for modulating the compartmentalization of calcium at synapses.