Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5

Ho Lee Jeong, Jinu Lee, Yeong Choi Kyu, Regine Hepp, Jae Youn Lee, Kyung Lim Mi, Mayumi Chatani-Hinze, Paul A. Roche, Goo Kim Dong, Soo Ahn Young, Hoon Kim Chul, Katherine W. Roche

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and synaptic plasticity. PKC regulates many aspects of mGluR function, including protein-protein interactions, Ca2+ signaling, and receptor desensitization. However, the mechanisms by which PKC regulates mGluR function are poorly understood. We have now identified calmodulin (CaM) as a dynamic regulator of mGluR5 trafficking. We show that the major PKC phosphorylation site on the intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of this residue is up-regulated in response to both receptor and PKC activation. In addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5 surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901 dramatically affects mGluR5 signaling by prolonging Ca2+ oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.

Original languageEnglish
Pages (from-to)12575-12580
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
Publication statusPublished - 2008 Aug 26

Fingerprint

Metabotropic Glutamate Receptors
Calmodulin
Phosphorylation
Serine
Neuronal Plasticity
G-Protein-Coupled Receptors
Synaptic Transmission
Neurotransmitter Agents
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Jeong, Ho Lee ; Lee, Jinu ; Kyu, Yeong Choi ; Hepp, Regine ; Lee, Jae Youn ; Mi, Kyung Lim ; Chatani-Hinze, Mayumi ; Roche, Paul A. ; Dong, Goo Kim ; Young, Soo Ahn ; Chul, Hoon Kim ; Roche, Katherine W. / Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 34. pp. 12575-12580.
@article{06d89c89f78d46448415d36e81f88f21,
title = "Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5",
abstract = "Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and synaptic plasticity. PKC regulates many aspects of mGluR function, including protein-protein interactions, Ca2+ signaling, and receptor desensitization. However, the mechanisms by which PKC regulates mGluR function are poorly understood. We have now identified calmodulin (CaM) as a dynamic regulator of mGluR5 trafficking. We show that the major PKC phosphorylation site on the intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of this residue is up-regulated in response to both receptor and PKC activation. In addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5 surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901 dramatically affects mGluR5 signaling by prolonging Ca2+ oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.",
author = "Jeong, {Ho Lee} and Jinu Lee and Kyu, {Yeong Choi} and Regine Hepp and Lee, {Jae Youn} and Mi, {Kyung Lim} and Mayumi Chatani-Hinze and Roche, {Paul A.} and Dong, {Goo Kim} and Young, {Soo Ahn} and Chul, {Hoon Kim} and Roche, {Katherine W.}",
year = "2008",
month = "8",
day = "26",
doi = "10.1073/pnas.0712033105",
language = "English",
volume = "105",
pages = "12575--12580",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "34",

}

Jeong, HL, Lee, J, Kyu, YC, Hepp, R, Lee, JY, Mi, KL, Chatani-Hinze, M, Roche, PA, Dong, GK, Young, SA, Chul, HK & Roche, KW 2008, 'Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 34, pp. 12575-12580. https://doi.org/10.1073/pnas.0712033105

Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. / Jeong, Ho Lee; Lee, Jinu; Kyu, Yeong Choi; Hepp, Regine; Lee, Jae Youn; Mi, Kyung Lim; Chatani-Hinze, Mayumi; Roche, Paul A.; Dong, Goo Kim; Young, Soo Ahn; Chul, Hoon Kim; Roche, Katherine W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 34, 26.08.2008, p. 12575-12580.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5

AU - Jeong, Ho Lee

AU - Lee, Jinu

AU - Kyu, Yeong Choi

AU - Hepp, Regine

AU - Lee, Jae Youn

AU - Mi, Kyung Lim

AU - Chatani-Hinze, Mayumi

AU - Roche, Paul A.

AU - Dong, Goo Kim

AU - Young, Soo Ahn

AU - Chul, Hoon Kim

AU - Roche, Katherine W.

PY - 2008/8/26

Y1 - 2008/8/26

N2 - Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and synaptic plasticity. PKC regulates many aspects of mGluR function, including protein-protein interactions, Ca2+ signaling, and receptor desensitization. However, the mechanisms by which PKC regulates mGluR function are poorly understood. We have now identified calmodulin (CaM) as a dynamic regulator of mGluR5 trafficking. We show that the major PKC phosphorylation site on the intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of this residue is up-regulated in response to both receptor and PKC activation. In addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5 surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901 dramatically affects mGluR5 signaling by prolonging Ca2+ oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.

AB - Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and synaptic plasticity. PKC regulates many aspects of mGluR function, including protein-protein interactions, Ca2+ signaling, and receptor desensitization. However, the mechanisms by which PKC regulates mGluR function are poorly understood. We have now identified calmodulin (CaM) as a dynamic regulator of mGluR5 trafficking. We show that the major PKC phosphorylation site on the intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of this residue is up-regulated in response to both receptor and PKC activation. In addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5 surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901 dramatically affects mGluR5 signaling by prolonging Ca2+ oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.

UR - http://www.scopus.com/inward/record.url?scp=50449083523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50449083523&partnerID=8YFLogxK

U2 - 10.1073/pnas.0712033105

DO - 10.1073/pnas.0712033105

M3 - Article

C2 - 18715999

AN - SCOPUS:50449083523

VL - 105

SP - 12575

EP - 12580

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 34

ER -