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Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus.

ABSTRACT: The mGluR-dependent endocytosis of AMPA receptors (AMPARs) in the CA1 region is protein synthesis dependent. However, why this form of trafficking, and not that mediated by NMDA receptor activation, is dependent on protein translation is unclear. Here we have studied the contribution of the cytoskeletal microtubule-associated protein 1B (MAP1B) to the pathway-specific internalization of AMPARs. Treatments of cultured neurons with 3,4-dihydroxyphenylglycol (DHPG) or NMDA, both of which drive AMPAR endocytosis, caused a translation-dependent increase in the dendritic levels of MAP1B protein. Although interfering with protein synthesis using short interfering RNA (siRNA) to eEF2 kinase (eukaryotic elongation factor 2 kinase) blocked the dendritic MAP1B increase by both pathways, it selectively blocked the DHPG- and not the NMDA-induced AMPAR endocytosis. In support of MAP1B synthesis contributing to metabotropic glutamate receptor (mGluR)-mediated AMPAR endocytosis, siRNA against MAP1B in CA1 cultured neurons specifically blocked the DHPG-induced AMPAR internalization. Previous studies suggest a direct interaction between MAP1B and the AMPAR-binding protein GRIP1. Biochemical studies establish that MAP1B associates with GRIP1 and forms a complex with GluR2 in vivo in rat hippocampus. Furthermore, the interaction between MAP1B and GRIP1 increased significantly in acute slices after treatment with DHPG and not NMDA. Together, these findings suggest that MAP1B plays a selective role in the DHPG-induced endocytosis of AMPARs, perhaps through its interaction with GRIP1.

SUBMITTER: Davidkova G

PROVIDER: S-EPMC6673406 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus.

Davidkova Genoveva G Carroll Reed C RC

The Journal of neuroscience : the official journal of the Society for Neuroscience 20071101 48

The mGluR-dependent endocytosis of AMPA receptors (AMPARs) in the CA1 region is protein synthesis dependent. However, why this form of trafficking, and not that mediated by NMDA receptor activation, is dependent on protein translation is unclear. Here we have studied the contribution of the cytoskeletal microtubule-associated protein 1B (MAP1B) to the pathway-specific internalization of AMPARs. Treatments of cultured neurons with 3,4-dihydroxyphenylglycol (DHPG) or NMDA, both of which drive AMPA ...[more]

PMID: 18045921

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Project description:1. Phospholipase D (PLD) is the key enzyme in a signal transduction pathway leading to the formation of the second messengers phosphatidic acid and diacylglycerol. In order to define the pharmacological profile of PLD-coupled metabotropic glutamate receptors (mGluRs), PLD activity was measured in slices of adult rat brain in the presence of mGluR agonists or antagonists. Activation of the phospholipase C (PLC) pathway by the same agents was also examined. 2. The mGluR-selective agonist (1S,3R)-l-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] induced a concentration-dependent (10-300 microM) activation of PLD in the hippocampus, neocortex, and striatum, but not in the cerebellum. The effect was particularly evident in hippocampal slices, which were thus used for all subsequent experiments. 3. The rank order of potencies for agonists stimulating the PLD response was: quisqualate > ibotenate > (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine > (1S,3R)-ACPD > L-cysteine sulphinic acid > L-aspartate > L-glutamate. L-(+)-2-Amino-4-phosphonobutyric acid and the ionotropic glutamate receptor agonists N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate failed to activate PLD. (RS)-3,5-dihydroxyphenylglycine (100300 microM), an agonist of mGluRs of the first group, stimulated PLC but inhibited the PLD response elicited by 100 microM (1S,3R)-ACPD. 4. (+)-alpha-Methyl-4-carboxyphenylglycine (0.1-1 mM), a competitive antagonist of mGluRs of the first and second group, elicited a significant PLD response. L-(+)-2-Amino-3-phosphonopropionic acid (1 mM), an antagonist of mGluRs of the first group, inhibited the 100 microM (1S,3R)-ACPD-induced PLC response but produced a robust stimulation of PLD. 5. 12-O-Tetradecanoylphorbol 13-acetic acid and phorbol 12,13-dibutyrate (PDBu), activators of protein kinase C, at 1 microM had a stimulatory effect on mGluRs linked to PLD but depressed (1S,3R)-ACPD-induced phosphoinositide hydrolysis. The protein kinase C inhibitor, staurosporine (1 and 10 microM) reduced PLD activation induced by 1 microM PDBu but not by 100 microM (1S,3R)-ACPD. 6. Our results suggest that PLD-linked mGluRs in rat hippocampus may be distinct from any known mGluR subtype coupled to PLC or adenylyl cyclase. Moreover, they indicate that independent mGluRs coupled to the PLC and PLD pathways exist and that mGluR agonists can stimulate PLD through a PKC-independent mechanism.

Dataset Information

Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus.

Publications

Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus.

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