Dlg4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-gene
Symbol: DLG4
Full Name: Discs Large Homolog 4
Chromosomal Location: 8p12
NCBI Gene ID: 1749
OMIM: 602887
Ensembl ID: ENSG00000132535
UniProt: P78352
Proteins: PSD-95
Associated Diseases: Alzheimer's Disease, Autism Spectrum Disorder, Schizophrenia, ALS, Huntington's Disease
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DLG4 (Discs Large Homolog 4) encodes PSD-95 (Postsynaptic Density Protein 95), one of the most abundant and important scaffolding proteins at excitatory synapses in the central nervous system. PSD-95 is a core component of the postsynaptic density, a specialized structure beneath the postsynaptic membrane that organizes signaling complexes essential for synaptic transmission, plasticity, and stability. PSD-95 belongs to the membrane-associated guanylate kinase (MAGUK) family and plays critical roles in anchoring receptors, ion channels, and signaling molecules at synapses. Loss or dysfunction of PSD-95 is strongly implicated in Alzheimer's disease, where synaptic failure is the strongest correlate of cognitive impairment.
PSD-95 contains multiple protein-interaction domains:
Three PDZ domains (PDZ1-3): Bind to C-terminal motifs of target proteins
One SH3 domain: Proline-rich region interactions
One GK domain (guanylate kinase-like): Enzyme-like fold without catalytic activity
PSD-95 forms dimers and tetramers through interactions at its N-terminus, enabling multivalent binding to synaptic partners.
PSD-95 serves as a central hub for synaptic protein networks:
Receptor anchoring
Ion channel clustering
Signaling complex assembly
Cytoskeletal links
PSD-95 is central to synaptic plasticity mechanisms:
PSD-95 shows region-specific expression:
PSD-95 is critically involved in AD pathogenesis:
Research findings:
The study of Dlg4 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Sheng M, Hoogenraad CC. "The postsynaptic architecture of excitatory synapses." Physiological Reviews (2007). PMID:17913920
Chen X, Nelson CD, Li X, et al. "PSD-95 is required to sustain the molecular organization of the postsynaptic density." Journal of Neuroscience (2011). PMID:21976534
Kim E, Sheng M. "PDZ domain proteins of synapses." Nature Reviews Neuroscience (2004). PMID:15494260
Gardoni F, Marcello E, Di Luca M. "Postsynaptic density-membrane associated guanylate kinase proteins as synaptic organizers." Journal of Chemistry (2010). PMID:20192780
Migaud M, Charlesworth P, Dempster M, et al. "Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein." Nature (1998). PMID:9690471
Hao J, Sheng H, Wang G, et al. "Altered synaptic development and plasticity in the dentate gyrus of DLG4 conditional knockout mice." Brain Structure and Function (2016). PMID:27164869
Sultana R, Butler J, Kim E, et al. "The expression of DLG4 isoforms in brain and its relationship with Alzheimer's disease." Neurochemical Research (2012). PMID:21948161
Cane M, Ronco F, Kuperstein G, et al. "DLG4 gene and synaptic signaling in neuropsychiatric disorders." Molecular Psychiatry (2019). PMID:31064762
Dickey CA, Loring JF, Montgomery J, et al. "Selectively reduced expression of synaptic scaffolding protein PSD-95 in Alzheimer disease." Brain Research (2003). PMID:12880916
Tu H, Noel S, Bohuslav J, et al. "Selective contribution of NMDARs to long-term memory formation." Neuropsychopharmacology (2019). PMID:30790318