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Differential changes in the phosphorylation of the protein kinase C substrates myristoylated alanine-rich C kinase substrate and growth-associated protein-43/B-50 following Schaffer collateral long-term potentiation and long-term depression.
J Neurochem 1999; 73(5):2175-83JN

Abstract

Activation of protein kinase C (PKC) is one of the biochemical pathways thought to be activated during activity-dependent synaptic plasticity in the brain, and long-term potentiation (LTP) and long-term depression (LTD) are two of the most extensively studied models of synaptic plasticity. Here we have examined changes in the in situ phosphorylation level of two major PKC substrates, myristoylated alanine-rich C kinase substrate (MARCKS) and growth-associated protein (GAP)-43/B-50, after pharmacological stimulation or induction of LTP or LTD in the CA1 field of the hippocampus. We find that direct PKC activation with phorbol esters, K+-induced depolarization, and activation of metabotropic glutamate receptors increase the in situ phosphorylation of both MARCKS and GAP-43/B-50. The induction of LTP increased the in situ phosphorylation of both MARCKS and GAP-43/B-50 at 10 min following high-frequency stimulation, but only GAP-43/B-50 phosphorylation remained elevated 60 min after LTP induction. Furthermore, blockade of LTP induction with the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid prevented elevations in GAP-43/B-50 phosphorylation but did not prevent the elevation in MARCKS phosphorylation 10 min following LTP induction. The induction of LTD resulted in a reduction in GAP-43/B-50 phosphorylation but did not affect MARCKS phosphorylation. Together these findings show that activity-dependent synaptic plasticity elicits PKC-mediated phosphorylation of substrate proteins in a highly selective and coordinated manner and demonstrate the compartmentalization of PKC-substrate interactions. Key Words: Protein kinase C-Myristoylated alanine-rich C kinase substrate-Growth-associated protein-43-Long-term potentiation-Long-term depression-(RS)-alpha-Methyl-4-carboxyphenylglycine-D-2-Amino-5-ph osphonopentanoic acid-Glutamate.

Authors+Show Affiliations

Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10537078

Citation

Ramakers, G M., et al. "Differential Changes in the Phosphorylation of the Protein Kinase C Substrates Myristoylated Alanine-rich C Kinase Substrate and Growth-associated protein-43/B-50 Following Schaffer Collateral Long-term Potentiation and Long-term Depression." Journal of Neurochemistry, vol. 73, no. 5, 1999, pp. 2175-83.
Ramakers GM, McNamara RK, Lenox RH, et al. Differential changes in the phosphorylation of the protein kinase C substrates myristoylated alanine-rich C kinase substrate and growth-associated protein-43/B-50 following Schaffer collateral long-term potentiation and long-term depression. J Neurochem. 1999;73(5):2175-83.
Ramakers, G. M., McNamara, R. K., Lenox, R. H., & De Graan, P. N. (1999). Differential changes in the phosphorylation of the protein kinase C substrates myristoylated alanine-rich C kinase substrate and growth-associated protein-43/B-50 following Schaffer collateral long-term potentiation and long-term depression. Journal of Neurochemistry, 73(5), pp. 2175-83.
Ramakers GM, et al. Differential Changes in the Phosphorylation of the Protein Kinase C Substrates Myristoylated Alanine-rich C Kinase Substrate and Growth-associated protein-43/B-50 Following Schaffer Collateral Long-term Potentiation and Long-term Depression. J Neurochem. 1999;73(5):2175-83. PubMed PMID: 10537078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential changes in the phosphorylation of the protein kinase C substrates myristoylated alanine-rich C kinase substrate and growth-associated protein-43/B-50 following Schaffer collateral long-term potentiation and long-term depression. AU - Ramakers,G M, AU - McNamara,R K, AU - Lenox,R H, AU - De Graan,P N, PY - 1999/10/28/pubmed PY - 1999/10/28/medline PY - 1999/10/28/entrez SP - 2175 EP - 83 JF - Journal of neurochemistry JO - J. Neurochem. VL - 73 IS - 5 N2 - Activation of protein kinase C (PKC) is one of the biochemical pathways thought to be activated during activity-dependent synaptic plasticity in the brain, and long-term potentiation (LTP) and long-term depression (LTD) are two of the most extensively studied models of synaptic plasticity. Here we have examined changes in the in situ phosphorylation level of two major PKC substrates, myristoylated alanine-rich C kinase substrate (MARCKS) and growth-associated protein (GAP)-43/B-50, after pharmacological stimulation or induction of LTP or LTD in the CA1 field of the hippocampus. We find that direct PKC activation with phorbol esters, K+-induced depolarization, and activation of metabotropic glutamate receptors increase the in situ phosphorylation of both MARCKS and GAP-43/B-50. The induction of LTP increased the in situ phosphorylation of both MARCKS and GAP-43/B-50 at 10 min following high-frequency stimulation, but only GAP-43/B-50 phosphorylation remained elevated 60 min after LTP induction. Furthermore, blockade of LTP induction with the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid prevented elevations in GAP-43/B-50 phosphorylation but did not prevent the elevation in MARCKS phosphorylation 10 min following LTP induction. The induction of LTD resulted in a reduction in GAP-43/B-50 phosphorylation but did not affect MARCKS phosphorylation. Together these findings show that activity-dependent synaptic plasticity elicits PKC-mediated phosphorylation of substrate proteins in a highly selective and coordinated manner and demonstrate the compartmentalization of PKC-substrate interactions. Key Words: Protein kinase C-Myristoylated alanine-rich C kinase substrate-Growth-associated protein-43-Long-term potentiation-Long-term depression-(RS)-alpha-Methyl-4-carboxyphenylglycine-D-2-Amino-5-ph osphonopentanoic acid-Glutamate. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/10537078/Differential_changes_in_the_phosphorylation_of_the_protein_kinase_C_substrates_myristoylated_alanine_rich_C_kinase_substrate_and_growth_associated_protein_43/B_50_following_Schaffer_collateral_long_term_potentiation_and_long_term_depression_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1999&volume=73&issue=5&spage=2175 DB - PRIME DP - Unbound Medicine ER -