Related Experiment Video
Updated: Jun 27, 2026
08:55
Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD
Clare M Gladding1, Valerie J Collett, Zhengping Jia
1Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol BS81TD, UK.
Molecular and Cellular Neurosciences
|December 10, 2008
Summary
Group I metabotropic glutamate receptor-dependent long-term depression (LTD) involves selective dephosphorylation of GluR2 AMPA receptor subunits, regulating receptor internalization in the hippocampus.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Biology
Background:
- Long-term depression (LTD) at hippocampal CA1 synapses can be induced by NMDA receptors (NMDARs) or group I metabotropic glutamate receptors (mGluRs).
- DHPG-induced LTD relies on postsynaptic protein tyrosine phosphatases (PTPs) that dephosphorylate AMPA receptors (AMPARs).
Purpose of the Study:
- To investigate the subunit selectivity of AMPAR dephosphorylation during DHPG-LTD versus NMDA-LTD.
- To determine the role of AMPAR subunit dephosphorylation in AMPAR internalization during DHPG-LTD.
Main Methods:
- Activation of hippocampal CA1 synapses using selective agonists NMDA and (RS)-3,5-dihydroxyphenylglycine (DHPG).
- Analysis of tyrosine phosphorylation status of endogenous AMPAR subunits (GluR1, GluR2, GluR3) and specific phosphorylation sites.
- Assessment of AMPAR endocytosis and its dependence on PTP activity.
Main Results:
- DHPG-LTD specifically dephosphorylates the GluR2 AMPAR subunit, while NMDA-LTD does not affect GluR2 tyrosine phosphorylation.
- NMDA-LTD, but not DHPG-LTD, is associated with dephosphorylation of GluR1-serine-845.
- PTP-dependent AMPAR endocytosis in DHPG-LTD involves the tyrosine dephosphorylation of cell surface AMPARs.
Conclusions:
- Subunit-selective tyrosine dephosphorylation of GluR2 is a key mechanism regulating AMPAR internalization during DHPG-LTD.
- Distinct molecular pathways govern AMPAR trafficking in DHPG-LTD and NMDA-LTD in the hippocampus.
Related Concept Videos
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...