Interaction between very-KIND Ras guanine exchange factor and microtubule-associated protein 2, and its role in dendrite growth - Structure and function of the second kinase noncatalytic C-lobe domain

Jinhong Huang, Asako Furuya, Kanehiro Hayashi, Teiichi Furuichi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The kinase noncatalytic C-lobe domain (KIND) is a putative protein-protein interaction module. Four KIND-containing proteins, Spir-2 (actin-nuclear factor), PTPN13 (protein tyrosine phosphatase), FRMPD2 (scaffold protein) and very-KIND (v-KIND) (brain-specific Ras guanine nucleotide exchange factor), have been identified to date. Uniquely, v-KIND has two KINDs (i.e. KIND1 and KIND2), whereas the other three proteins have only one. The functional role of KIND, however, remains unclear. We previously demonstrated that v-KIND interacts with the high-molecular weight microtubule-associated protein 2 (MAP2), a dendritic microtubule-associated protein, leading to negative regulation of neuronal dendrite growth. In the present study, we analyzed the structure-function relationships of the v-KIND-MAP2 interaction by generating a series of mutant constructs. The interaction with endogenous MAP2 in mouse cerebellar granule cells was specific to v-KIND KIND2, but not KIND1, and was not observed for the KINDs from other KIND-containing proteins. The binding core modules critical for the v-KIND-MAP2 interaction were defined within 32 residues of the mouse v-KIND KIND2 and 43 residues of the mouse MAP2 central domain. Three Leu residues at amino acid positions 461, 474 and 477 in the MAP2-binding core module of KIND2 contributed to the interaction. The MAP2-binding core module itself promoted dendrite branching as a dominant-negative regulator of v-KIND in hippocampal neurons. The results reported in the present study demonstrate the structural and functional determinant underlying the v-KIND-MAP2 interaction that controls dendrite arborization patterns. Structured digital abstract to by with by,) with by with by with by The brain-specific Ras guanine exchange factor (RasGEF) very-kinase noncatalytic C-lobe domain (KIND) regulates neuronal dendrite growth by interacting with the high-molecular weight microtubule-associated protein 2 (MAP2). We describe the structural and functional determinants of the protein-protein interaction between very-KIND and MAP2. We suggest that the MAP2-binding core module of very-KIND is involved in negative regulation of dendrite branching in hippocampal neurons and cerebellar granule cells

Original languageEnglish
Pages (from-to)1651-1661
Number of pages11
JournalFEBS Journal
Volume278
Issue number10
DOIs
Publication statusPublished - 2011 May
Externally publishedYes

Fingerprint

Microtubule-Associated Proteins
Guanine
Dendrites
Phosphotransferases
Growth
Proteins
Protein Binding
ras Guanine Nucleotide Exchange Factors
Neurons
Brain
Molecular Weight
Molecular weight
Neuronal Plasticity
Protein Tyrosine Phosphatases
Protein Kinases
Scaffolds
Actins
Amino Acids

Keywords

  • dendrite growth
  • KIND domain
  • MAP2
  • protein-protein interaction
  • RasGEF

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

@article{b6bef6a71dc24f119783241f5ddf41b7,
title = "Interaction between very-KIND Ras guanine exchange factor and microtubule-associated protein 2, and its role in dendrite growth - Structure and function of the second kinase noncatalytic C-lobe domain",
abstract = "The kinase noncatalytic C-lobe domain (KIND) is a putative protein-protein interaction module. Four KIND-containing proteins, Spir-2 (actin-nuclear factor), PTPN13 (protein tyrosine phosphatase), FRMPD2 (scaffold protein) and very-KIND (v-KIND) (brain-specific Ras guanine nucleotide exchange factor), have been identified to date. Uniquely, v-KIND has two KINDs (i.e. KIND1 and KIND2), whereas the other three proteins have only one. The functional role of KIND, however, remains unclear. We previously demonstrated that v-KIND interacts with the high-molecular weight microtubule-associated protein 2 (MAP2), a dendritic microtubule-associated protein, leading to negative regulation of neuronal dendrite growth. In the present study, we analyzed the structure-function relationships of the v-KIND-MAP2 interaction by generating a series of mutant constructs. The interaction with endogenous MAP2 in mouse cerebellar granule cells was specific to v-KIND KIND2, but not KIND1, and was not observed for the KINDs from other KIND-containing proteins. The binding core modules critical for the v-KIND-MAP2 interaction were defined within 32 residues of the mouse v-KIND KIND2 and 43 residues of the mouse MAP2 central domain. Three Leu residues at amino acid positions 461, 474 and 477 in the MAP2-binding core module of KIND2 contributed to the interaction. The MAP2-binding core module itself promoted dendrite branching as a dominant-negative regulator of v-KIND in hippocampal neurons. The results reported in the present study demonstrate the structural and functional determinant underlying the v-KIND-MAP2 interaction that controls dendrite arborization patterns. Structured digital abstract to by with by,) with by with by with by The brain-specific Ras guanine exchange factor (RasGEF) very-kinase noncatalytic C-lobe domain (KIND) regulates neuronal dendrite growth by interacting with the high-molecular weight microtubule-associated protein 2 (MAP2). We describe the structural and functional determinants of the protein-protein interaction between very-KIND and MAP2. We suggest that the MAP2-binding core module of very-KIND is involved in negative regulation of dendrite branching in hippocampal neurons and cerebellar granule cells",
keywords = "dendrite growth, KIND domain, MAP2, protein-protein interaction, RasGEF",
author = "Jinhong Huang and Asako Furuya and Kanehiro Hayashi and Teiichi Furuichi",
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T1 - Interaction between very-KIND Ras guanine exchange factor and microtubule-associated protein 2, and its role in dendrite growth - Structure and function of the second kinase noncatalytic C-lobe domain

AU - Huang, Jinhong

AU - Furuya, Asako

AU - Hayashi, Kanehiro

AU - Furuichi, Teiichi

PY - 2011/5

Y1 - 2011/5

N2 - The kinase noncatalytic C-lobe domain (KIND) is a putative protein-protein interaction module. Four KIND-containing proteins, Spir-2 (actin-nuclear factor), PTPN13 (protein tyrosine phosphatase), FRMPD2 (scaffold protein) and very-KIND (v-KIND) (brain-specific Ras guanine nucleotide exchange factor), have been identified to date. Uniquely, v-KIND has two KINDs (i.e. KIND1 and KIND2), whereas the other three proteins have only one. The functional role of KIND, however, remains unclear. We previously demonstrated that v-KIND interacts with the high-molecular weight microtubule-associated protein 2 (MAP2), a dendritic microtubule-associated protein, leading to negative regulation of neuronal dendrite growth. In the present study, we analyzed the structure-function relationships of the v-KIND-MAP2 interaction by generating a series of mutant constructs. The interaction with endogenous MAP2 in mouse cerebellar granule cells was specific to v-KIND KIND2, but not KIND1, and was not observed for the KINDs from other KIND-containing proteins. The binding core modules critical for the v-KIND-MAP2 interaction were defined within 32 residues of the mouse v-KIND KIND2 and 43 residues of the mouse MAP2 central domain. Three Leu residues at amino acid positions 461, 474 and 477 in the MAP2-binding core module of KIND2 contributed to the interaction. The MAP2-binding core module itself promoted dendrite branching as a dominant-negative regulator of v-KIND in hippocampal neurons. The results reported in the present study demonstrate the structural and functional determinant underlying the v-KIND-MAP2 interaction that controls dendrite arborization patterns. Structured digital abstract to by with by,) with by with by with by The brain-specific Ras guanine exchange factor (RasGEF) very-kinase noncatalytic C-lobe domain (KIND) regulates neuronal dendrite growth by interacting with the high-molecular weight microtubule-associated protein 2 (MAP2). We describe the structural and functional determinants of the protein-protein interaction between very-KIND and MAP2. We suggest that the MAP2-binding core module of very-KIND is involved in negative regulation of dendrite branching in hippocampal neurons and cerebellar granule cells

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