Inositol 1,4,5-Trisphosphate 3-Kinase A Is a Novel Microtubule-associated Protein

Abstract

Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a brain specificandF-actin-binding protein.Werecently demonstrated that IP3K-A modulates a structural reorganization of dendritic spines through F-actin remodeling, which is required for synap- tic plasticity and memory formation in brain. However, detailed functions of IP3K-A and its regulatory mechanisms involved in the neuronal cytoskeletal dynamics still remainunknown.In the present study, we identified tubulin as a candidate of IP3K-A- binding protein through proteomic screening. By various in vitro and in vivo approaches, we demonstrated that IP3K-A was a novel microtubule-associated protein (MAP), and the N ter- minus of IP3K-A was a critical region for direct binding to tubu- lin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP3K-A, leading to a significant reduction of microtubule binding affinity. These results suggest that PKA-dependent phosphorylation and microtubule binding of IP3K-A are involved in its regulatory mechanism for activity- dependent neuronal events such as local calcium signaling and its synaptic targeting.