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 [1]
Symbol: DLG4 [2]
Full Name: Discs Large Homolog 4 [3]
Chromosomal Location: 8p12 [4]
NCBI Gene ID: 1749 [5]
OMIM: 602887 [6]
Ensembl ID: ENSG00000132535 [7]
UniProt: P78352 [8]
Proteins: PSD-95 [9]
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.
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). Journal of Neuroscience. 2011. ↩︎
Kim E, Sheng M. "PDZ domain proteins of synapses." Nature Reviews Neuroscience (2004). Nature Reviews Neuroscience. 2004. ↩︎
Gardoni F, Marcello E, Di Luca M. "Postsynaptic density-membrane associated guanylate kinase proteins as synaptic organizers." Journal of Chemistry (2010). Journal of Chemistry. 2010. ↩︎
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). Nature. 1998. ↩︎
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). Brain Structure and Function. 2016. ↩︎
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). Neurochemical Research. 2012. ↩︎
Cane M, Ronco F, Kuperstein G, et al. "DLG4 gene and synaptic signaling in neuropsychiatric disorders." Molecular Psychiatry (2019). Molecular Psychiatry. 2019. ↩︎
Dickey CA, Loring JF, Montgomery J, et al. "Selectively reduced expression of synaptic scaffolding protein PSD-95 in Alzheimer disease." Brain Research (2003). Brain Research. 2003. ↩︎
Tu H, Noel S, Bohuslav J, et al. "Selective contribution of NMDARs to long-term memory formation." Neuropsychopharmacology (2019). Neuropsychopharmacology. 2019. ↩︎