Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein

PKA-dependent phosphoregulation of microtubule binding affinity

Dongmin Lee, Hyun Woo Lee, Soontaek Hong, Byung Il Choi, Hyun Wook Kim, Seung Baek Han, Il Hwan Kim, Jin Young Bae, Yong Chul Bae, Im Joo Rhyu, Woong Sun, Hyun Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a brain specific and F-actin-binding protein. Werecently demonstrated that IP 3K-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 IP3K-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 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 terminus of IP3K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP 3K-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.

Original languageEnglish (US)
Pages (from-to)15981-15995
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number19
DOIs
StatePublished - May 4 2012

Fingerprint

Inositol 1,4,5-trisphosphate 3-kinase
Microtubule-Associated Proteins
Microtubules
Phosphotransferases
Tubulin
Brain
Dendritic Spines
Phosphorylation
Neuronal Plasticity
Calcium Signaling
Proteomics
Neurons
Plasticity
Actins
Carrier Proteins
Screening
Calcium
Data storage equipment

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein : PKA-dependent phosphoregulation of microtubule binding affinity. / Lee, Dongmin; Lee, Hyun Woo; Hong, Soontaek; Choi, Byung Il; Kim, Hyun Wook; Han, Seung Baek; Kim, Il Hwan; Bae, Jin Young; Bae, Yong Chul; Rhyu, Im Joo; Sun, Woong; Kim, Hyun.

In: Journal of Biological Chemistry, Vol. 287, No. 19, 04.05.2012, p. 15981-15995.

Research output: Contribution to journalArticle

Lee, Dongmin ; Lee, Hyun Woo ; Hong, Soontaek ; Choi, Byung Il ; Kim, Hyun Wook ; Han, Seung Baek ; Kim, Il Hwan ; Bae, Jin Young ; Bae, Yong Chul ; Rhyu, Im Joo ; Sun, Woong ; Kim, Hyun. / Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein : PKA-dependent phosphoregulation of microtubule binding affinity. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 19. pp. 15981-15995.
@article{ab30374dab6145998a40fb5d7a35261a,
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 (IP3K-A) is a brain specific and F-actin-binding protein. Werecently demonstrated that IP 3K-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 IP3K-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 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 terminus of IP3K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP 3K-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.",
author = "Dongmin Lee and Lee, {Hyun Woo} and Soontaek Hong and Choi, {Byung Il} and Kim, {Hyun Wook} and Han, {Seung Baek} and Kim, {Il Hwan} and Bae, {Jin Young} and Bae, {Yong Chul} and Rhyu, {Im Joo} and Woong Sun and Hyun Kim",
year = "2012",
month = "5",
day = "4",
doi = "10.1074/jbc.M112.344101",
language = "English (US)",
volume = "287",
pages = "15981--15995",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "19",

}

TY - JOUR

T1 - Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein

T2 - PKA-dependent phosphoregulation of microtubule binding affinity

AU - Lee, Dongmin

AU - Lee, Hyun Woo

AU - Hong, Soontaek

AU - Choi, Byung Il

AU - Kim, Hyun Wook

AU - Han, Seung Baek

AU - Kim, Il Hwan

AU - Bae, Jin Young

AU - Bae, Yong Chul

AU - Rhyu, Im Joo

AU - Sun, Woong

AU - Kim, Hyun

PY - 2012/5/4

Y1 - 2012/5/4

N2 - Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a brain specific and F-actin-binding protein. Werecently demonstrated that IP 3K-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 IP3K-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 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 terminus of IP3K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP 3K-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.

AB - Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a brain specific and F-actin-binding protein. Werecently demonstrated that IP 3K-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 IP3K-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 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 terminus of IP3K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP 3K-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.

UR - http://www.scopus.com/inward/record.url?scp=84860847552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860847552&partnerID=8YFLogxK

U2 - 10.1074/jbc.M112.344101

DO - 10.1074/jbc.M112.344101

M3 - Article

VL - 287

SP - 15981

EP - 15995

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 19

ER -