Glutamate Receptors and Synaptic Scaffolding

Flashcards covering the molecular structure, protein-protein interactions, and physiological functions of glutamate receptors and their associated scaffolding proteins at the synapse.

Long Term Potentiation (LTP)

A form of synaptic plasticity characterized by a persistent increase in synaptic strength, typically induced by high-frequency stimulation (e.g., $100\,Hz$ for $1\,s$).

Long Term Depression (LTD)

A form of synaptic plasticity characterized by a persistent decrease in synaptic strength, typically induced by low-frequency stimulation (e.g., $5\,Hz$ for $3\,min$ given twice).

Glutamate Receptor C-terminus

The intracellular tail of both ionotropic and metabotropic glutamate receptors that acts as a site for protein-protein interactions and phosphorylation by protein kinases.

PSD-95 (Postsynaptic Density Protein-95)

A member of the MAGUK family of proteins that contains multiple PDZ domains; it binds to NMDA receptors and anchors them to the postsynaptic density.

PDZ Domains

Protein interaction modules of approximately 100 amino acids (GLGF repeats) that recognize specific sequences at the extreme carboxyl-terminus (C-terminus) of target proteins.

T/SXV Motif

A terminal amino acid sequence (Threonine or Serine, Any Amino Acid, Valine) that binds to the second PDZ domain of the scaffolding protein PSD-95.

Yeast Two Hybrid (Y2H)

A scientific strategy used to identify protein-protein interactions, such as identifying PSD-95 as a binding partner for the NR2B (GluN2B) subunits of NMDA receptors.

TARPs (Transmembrane AMPA receptor Regulatory Proteins)

A family of membrane-spanning proteins, including Stargazin, that interact with AMPA receptors to ensure their delivery to and anchoring at the postsynaptic site.

Stargazer Mouse

A mutant mouse model used to test protein function, which exhibits motor defects and lacks functional AMPA receptor clustering due to the absence of the protein Stargazin.

GRIP (Glutamate Receptor Interacting Protein)

A PDZ scaffold protein containing seven PDZ domains that interacts with the C-termini of GluA2 and GluA3 AMPA receptor subunits, specifically through PDZ domains 4-6.

PICK1 (Protein Interacting with C Kinase 1)

A protein with a single PDZ domain that interacts with GluA2 and GluA3; it also interacts with protein kinase C $\alpha$ and is involved in AMPA receptor regulation.

Serine 880 ($S880$)

A phosphorylation site on the GluA2 subunit; its phosphorylation by PKC regulates binding to GRIP and PICK1 and is linked to AMPA receptor internalisation during LTD.

Serine 845 ($S845$)

A phosphorylation site on the GluA1 subunit that, when phosphorylated by PKA or via CGKII, increases AMPA receptor currents and synaptic recruitment.

Homer

A synaptic scaffolding protein that binds to metabotropic glutamate receptors (mGluRs) via a domain similar to EVH1; it is rapidly induced by synaptic activity.

Homer 1a (Homer IEG)

An immediate early gene variant of Homer that lacks the coiled-coil domain required for multimerization; it is upregulated by activity and mediates homeostatic synaptic down-scaling during sleep.

nNOS (neuronal Nitric Oxide Synthase)

An enzyme that produces nitric oxide ($NO$) in response to increased $[Ca^{2+}]_{in}$; it is coupled to NMDA receptors via the second PDZ domain of PSD-95.

EVH1 Domain

A protein interaction domain found in Homer proteins that binds to proline-rich sequences ($PPxxFR$) in target proteins like mGluR5.

Co-immunoprecipitation (Co-IP)

A scientific technique used to verify protein complexes in the brain by using specific antibodies to precipitate a target protein along with its associated binding partners.