Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene. [5] [6]
Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene. [5] [6]
Chapsyn-110/PSD-93 a member of the membrane-associated guanylate kinase (MAGUK) family. The protein forms a heterodimer with a related family member that may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Alternatively spliced transcript variants encoding distinct isoforms have been described but their full-length nature has yet to be completely determined. [7]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Abnormal [8] |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Prepulse inhibition | Normal |
| Indirect calorimetry | Abnormal [9] |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Abnormal [10] |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal [11] |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal |
| Citrobacter infection | Abnormal [12] |
| All tests and analysis from [13] [14] |
Model organisms have been used in the study of DLG2 function. A knockout mouse line, called Dlg2tm1Dsb was generated. [15] [16] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [13] [17] Twenty four tests were carried out on homozygous mutant mice and five significant abnormalities were observed. [13] Both sexes had atypical indirect calorimetry and DEXA parameters. Females also had decreased body weight, decreased circulating HDL cholesterol levels, and increased susceptibility to bacterial infection. [13]
DLG2 has been shown to interact with GRIN2B, [18] [19] KCNJ12. [20]
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the central nervous system (CNS). It has been traditionally classified as a non-NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. The receptor was first named the "quisqualate receptor" by Watkins and colleagues after a naturally occurring agonist quisqualate and was only later given the label "AMPA receptor" after the selective agonist developed by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The GRIA2-encoded AMPA receptor ligand binding core was the first glutamate receptor ion channel domain to be crystallized.
The postsynaptic density (PSD) is a protein dense specialization attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in close apposition to the presynaptic active zone and ensures that receptors are in close proximity to presynaptic neurotransmitter release sites. PSDs vary in size and composition among brain regions, and have been studied in great detail at glutamatergic synapses. Hundreds of proteins have been identified in the postsynaptic density, including glutamate receptors, scaffold proteins, and many signaling molecules.
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes. PDZ domains also play a highly significant role in the anchoring of cell surface receptors to the actin cytoskeleton via mediators like NHERF and ezrin.
PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene.
Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the SAP97 gene.
Protein Interacting with C Kinase - 1 is a protein that in humans is encoded by the PICK1 gene.
Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.
Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B, is a protein that in humans is encoded by the GRIN2B gene.
Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.
Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded by the CACNG2 gene.
Disks large-associated protein 1 (DAP-1), also known as guanylate kinase-associated protein (GKAP), is a protein that in humans is encoded by the DLGAP1 gene. DAP-1 is known to be highly enriched in synaptosomal preparations of the brain, and present in the post-synaptic density.
SH3 and multiple ankyrin repeat domains protein 1 is a protein that in humans is encoded by the SHANK1 gene.
Lin-7 homolog A is a protein that in humans is encoded by the LIN7A gene.
Disks large-associated protein 4 (DAP-4) also known as SAP90/PSD-95-associated protein 4 (SAPAP-4) is a protein that in humans is encoded by the DLGAP4 gene.
Lin-7 homolog B is a protein that in humans is encoded by the LIN7B gene.
Glutamate receptor-interacting protein 2 is a protein that in humans is encoded by the GRIP2 gene.
Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene.
Cysteine-rich PDZ-binding protein is a protein that in humans is encoded by the CRIPT gene.
Mary Bernadette Kennedy is an American biochemist and neuroscientist. She is a member of the American Academy of Arts and Sciences, and is the Allen and Lenabelle Davis Professor of Biology at the California Institute of Technology, where she has been a member of the faculty since 1981. Her research focuses on the molecular mechanisms of synaptic plasticity, the process underlying formation of memory in the central nervous system. Her lab uses biochemical and molecular biological methods to study the protein machinery within a structure called the postsynaptic density. Kennedy has published over 100 papers with over 20,000 total citations.
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