DLG4
GeneName
DLG4
Summary
DLG4, also known as PSD-95, PSD95, or SAP90, is an 80kDa scaffolding protein predominantly expressed in the postsynaptic density of excitatory synapses in neurons. It plays a critical role in the clustering and regulation of AMPA and NMDA glutamate receptors, thereby influencing synaptic transmission and plasticity. DLG4 is localised at various cellular components including dendritic spines, synapses, and the plasma membrane, and is involved in processes such as cell-cell adhesion and dendritic spine morphogenesis. Its interactions with other proteins, including ionotropic glutamate receptors and neuroligins, facilitate the establishment of synaptic architecture and function.
Importance
DLG4 is relevant to: - Neurodevelopmental disorders, as it is implicated in synaptic maturation and plasticity essential for learning and memory - Neurodegenerative diseases, where dysregulation of synaptic proteins can lead to cognitive decline - Psychiatric disorders, given its role in synaptic transmission and behaviour regulation - Research into synaptic function and structure, providing insights into the mechanisms underlying synaptic connectivity and signal transduction
Top Products
For researchers investigating DLG4, we highly recommend the well-cited polyclonal antibody, Anti-PSD95 antibody - Synaptic Marker (ab18258). This antibody has garnered 472 citations, underscoring its reliability and trust within the scientific community. It has been validated in knockout models, ensuring its effectiveness in various applications, including Western blotting (WB), immunocytochemistry (ICC), and immunohistochemistry (IHC). This makes it an excellent choice for those looking to study DLG4 with confidence in their results. The Anti-PSD95 antibody [7E3-1B8] - Synaptic Marker ELISA Kit (ab13552), with 69 citations, is an excellent option for researchers looking to accurately measure DLG4 in their studies.
Abcam Product Citation Summary
The data indicates that DLG4 is being extensively studied in various contexts related to neuronal health and function, particularly in models of synaptic integrity, epilepsy, and neurodegenerative conditions. The use of multiple species, including mouse and rat, highlights the relevance of these studies in understanding the role of DLG4 in synaptic scaffolding and neuronal stability.
Abcam Product Citation Table
Domain
The PDZ domain 3 mediates interaction with ADR1B.
The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density.
Function
Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723).
Involvement in disease
Intellectual developmental disorder, autosomal dominant 62
MRD62
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Palmitoylated (PubMed:26701913). Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses (By similarity). Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering (By similarity). Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis (By similarity). Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering (By similarity). Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:26701913). Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons (By similarity).
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.
Sequence Similarities
Belongs to the MAGUK family.
Tissue Specificity
Brain.
Cellular localization
- Cell membrane
- Lipid-anchor
- Cytoplasmic side
- Postsynaptic density
- Synapse
- Cytoplasm
- Cell projection
- Axon
- Cell projection
- Dendritic spine
- Cell projection
- Dendrite
- Presynapse
- High levels in postsynaptic density of neurons in the forebrain. Also in presynaptic region of inhibitory synapses formed by cerebellar basket cells on axon hillocks of Purkinje cells. Suppression of neuronal activity induces synaptic accumulation and clustering of DLG4.
Alternative names
PSD95, DLG4, Disks large homolog 4, Postsynaptic density protein 95, Synapse-associated protein 90, PSD-95, SAP-90, SAP90