title: Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein: PKA-dependent phosphoregulation of microtubule binding affinity.
abstract: Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) is a brain specific and F-actin-binding protein. We recently demonstrated that IP(3)K-A modulates a structural reorganization of dendritic spines through F-actin remodeling, which is required for synaptic plasticity and memory formation in brain. However, detailed functions of IP(3)K-A and its regulatory mechanisms involved in the neuronal cytoskeletal dynamics still remain unknown. In the present study, we identified tubulin as a candidate of IP(3)K-A-binding protein through proteomic screening. By various in vitro and in vivo approaches, we demonstrated that IP(3)K-A was a novel microtubule-associated protein (MAP), and the N terminus of IP(3)K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP(3)K-A, leading to a significant reduction of microtubule binding affinity. These results suggest that PKA-dependent phosphorylation and microtubule binding of IP(3)K-A are involved in its regulatory mechanism for activity-dependent neuronal events such as local calcium signaling and its synaptic targeting.
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Brain Korea 21, Seoul 136-705, Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Soontaek
authors.initials: S
authors.lastname: Hong
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Choi
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Seung Baek
authors.initials: SB
authors.lastname: Han
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.forename: Im Joo
authors.initials: IJ
authors.lastname: Rhyu
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008297:Male; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D012694:Serine; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D017868:Cyclic AMP-Dependent Protein Kinases