Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5.

Proceedings of the National Academy of Sciences of the United States of America
Jeong Ho LeeK Roche

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, Ca(2+) 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 Ca(2+) oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.

References

Nov 8, 1996·The Journal of Biological Chemistry·T T ChuangA De Blasi
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·P J Conn, J P Pin
Feb 13, 1999·The Journal of Biological Chemistry·G J Della RoccaJ R Raymond
Jul 27, 1999·The Journal of Biological Chemistry·D WangJ M Quillan
Jun 30, 2001·Trends in Pharmacological Sciences·W P SpoorenR Kuhn
May 4, 2004·Trends in Pharmacological Sciences·Paul J Kenny, Athina Markou
Jun 29, 2004·Trends in Neurosciences·Mark F BearStephen T Warren
Jul 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gabriela LavezzariKatherine W Roche
Apr 2, 2005·Nature Reviews. Neuroscience·Zhengui Xia, Daniel R Storm
May 17, 2005·The Journal of Biological Chemistry·Chul Hoon KimKatherine W Roche
Dec 26, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Ralf Enz
Aug 1, 2007·Journal of Neuroscience Research·Chul Hoon KimKatherine W Roche
Dec 21, 2007·Neuron·Gül DölenMark F Bear

❮ Previous
Next ❯

Citations

Nov 26, 2009·Nature Reviews. Molecular Cell Biology·Stefanie L Ritter, Randy A Hall
Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kyu Yeong ChoiKatherine W Roche
Sep 1, 2009·The Journal of Biological Chemistry·Lucimar T FerreiraStephen S G Ferguson
Sep 10, 2010·The Journal of Biological Chemistry·Yun HuangJenny J Yang
Nov 21, 2009·Pharmacological Reviews·Clare M GladdingElek Molnár
Feb 26, 2010·Molecular Brain·Alexander A NicodemoStephen S G Ferguson
Oct 8, 2011·PloS One·Juan Camilo Gómez-PosadaAlvaro Villarroel
Nov 16, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suk Jin KoKatherine W Roche
Feb 22, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dao-Zhong JinJohn Q Wang
Apr 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kyu Yeong ChoiKatherine W Roche
Jul 25, 2009·Journal of Neurochemistry·Yun Hwa HongSang Jeong Kim
Mar 19, 2016·The International Journal of Biochemistry & Cell Biology·Samarjit Bhattacharyya
Jun 28, 2011·British Journal of Pharmacology·Ana C MagalhaesStephen Sg Ferguson
Dec 21, 2012·Neuroscience and Biobehavioral Reviews·Natalie Matosin, Kelly A Newell
May 24, 2016·Neuropharmacology·Kai Chang, Katherine W Roche
Oct 1, 2016·BMC Biology·Suhyoung Bahk, Walton D Jones
Mar 25, 2017·International Journal of Molecular Sciences·Juan ZouJenny J Yang
Jun 11, 2011·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jinu LeeChul Hoon Kim
Oct 19, 2014·Molecular Pharmacology·Yuh-Jiin I JongKaren L O'Malley
Aug 23, 2016·Journal of Neuroscience Research·Marek Schwendt, M Foster Olive
Dec 5, 2019·Frontiers in Molecular Neuroscience·Jeffri S RetamalNicholas A Veldhuis
Apr 26, 2016·Metallomics : Integrated Biometal Science·Rakshya GorkhaliJenny J Yang
Feb 19, 2011·Communicative & Integrative Biology·Hong WangMarc Flajolet

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.