The DLGAP family: neuronal expression, function and role in brain disorders
Open accessAbstract
The neurotransmitter glutamate facilitates neuronal signalling at excitatory synapses. Glutamate is released from the presynaptic membrane into the synaptic cleft. Across the synaptic cleft glutamate binds to both ion channels and metabotropic glutamate receptors at the postsynapse, which expedite downstream signalling in the neuron. The postsynaptic density, a highly specialized matrix, which is attached to the postsynaptic membrane, controls this downstream signalling. The postsynaptic density also resets the synapse after each synaptic firing. It is composed of numerous proteins including a family of Discs large associated protein 1, 2, 3 and 4 (DLGAP1-4) that act as scaffold proteins in the postsynaptic density. They link the glutamate receptors in the postsynaptic membrane to other glutamate receptors, to signalling proteins and to components of the cytoskeleton. With the central localisation in the postsynapse, the DLGAP family seems to play a vital role in synaptic scaling by regulating the turnover of both ionotropic and metabotropic glutamate receptors in response to synaptic activity. DLGAP family has been directly linked to a variety of psychological and neurological disorders. In this review we focus on the direct and indirect role of DLGAP family on schizophrenia as well as other brain diseases.
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In the cell-type-specific networks, the authors found well-known transcription factors associated with brain development, including NEUROG1, DLGAP2, and MEF2A for excitatory neurons and GAD1, GAD2, and LHX6 for inhibitory neurons.
“In these, we found a number of well-known TFs associated with brain development—e.g., NEUROG1, DLGAP2, and MEF2A for excitatory neurons and GAD1, GAD2, and LHX6 for inhibitory neurons (Fig. 5G) (43–46).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [44]
The postsynaptic density (PSD) harbors excitatory neurotransmitter receptors and essential structural proteins including SAPAP3.
“The postsynaptic density (PSD) harbors excitatory neurotransmitter receptors and essential structural proteins including the SAP90/PSD95-associated protein 3 (SAPAP3, also DLGAP3 or GKAP3) [6].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [6]
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Comprehensive functional genomic resource and integrative model for the human brain
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- Authors
- Rasmussen, A. H., Rasmussen, H. B., & Silahtaroglu, A.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Silahtaroglu, Asli
- Venue
- Molecular Brain
- Published
- 2017-09-04
- Volume
- 10
- Issue
- 1
- Pages
- 43-43
- ISSN
- 1756-6606 (ISSN-L)
- PMC
- PMC5583998
- OpenAlex
- W2750696266
- Cited by
- 234
- References
- 126
- Citations by year
- 2026: 25 · 2025: 31 · 2024: 43 · 2023: 32 · 2022: 24 · 2021: 29 · 2020: 27 · 2019: 12 · 2018: 9 · 2017: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Brain (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Lundbeckfonden (R77-A6365)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- postsynaptic density, synaptic scaffolding proteins, glutamate receptors, synaptic scaling, ionotropic glutamate receptors, metabotropic glutamate receptors, schizophrenia, brain disorders, neuronal signaling
- MeSH terms
- SAP90-PSD95 Associated Proteins, Amino Acid Sequence, Animals, Brain, Brain Diseases, Humans, Models, Biological, Neurons, Protein Interaction Mapping
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