git1

git1

Scaffold protein that organizes signaling complexes at synapses, crucial for synaptic plasticity, dendritic spine morphology, and neuronal migration.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">GIT1 — G Protein-Coupled Receptor Kinase Interactor 1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>GIT1</td></tr>
<tr><td><strong>Full Name</strong></td><td>G Protein-Coupled Receptor Kinase Interactor 1</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17p11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[28964](https://www.ncbi.nlm.nih.gov/gene/28964)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608036](https://www.omim.org/entry/608036)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000108226](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000108226)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9Y2J8](https://www.uniprot.org/uniprot/Q9Y2J8)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

git1

Scaffold protein that organizes signaling complexes at synapses, crucial for synaptic plasticity, dendritic spine morphology, and neuronal migration.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">GIT1 — G Protein-Coupled Receptor Kinase Interactor 1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>GIT1</td></tr>
<tr><td><strong>Full Name</strong></td><td>G Protein-Coupled Receptor Kinase Interactor 1</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17p11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[28964](https://www.ncbi.nlm.nih.gov/gene/28964)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608036](https://www.omim.org/entry/608036)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000108226](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000108226)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9Y2J8](https://www.uniprot.org/uniprot/Q9Y2J8)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

Scaffold is a human gene whose product the GIT1 gene encodes the G protein-coupled receptor kinase interactor 1, a multidomain scaffold protein that localizes to synaptic structures and plays critical roles in synaptic plasticity, spine morphology, and neuronal signaling[@git2005]. Variants in Scaffold have been implicated in Autism Spectrum Disorder, Intellectual Disability, Schizophrenia. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

The GIT1 gene encodes the G protein-coupled receptor kinase interactor 1, a multidomain scaffold protein that localizes to synaptic structures and plays critical roles in synaptic plasticity, spine morphology, and neuronal signaling[@git2005].

Scaffold Function

GIT1 serves as a scaffold protein that brings together multiple signaling molecules at discrete cellular locations. It contains multiple protein-interaction domains including:

• Ankyrin repeats for protein binding
• A PSD-95/Dlg/ZO-1 (PDZ) domain
• A Sponge domain for additional interactions
• A paxillin-binding domain (PBD)[@kim2011]

Synaptic Plasticity

GIT1[@git2005] is enriched in [dendritic spines](/mechanisms/dendritic-spines) and synapses, where it regulates:

• AMPA receptor trafficking: GIT1 interacts with GRIP1 and regulates AMPA receptor internalization during long-term depression (LTD)[@ko2003]
• [NMDA receptor](/entities/nmda-receptor) signaling: GIT1 modulates NMDA receptor-mediated calcium influx and downstream signaling
• Dendritic spine morphology: GIT1 regulates spine size and number through interactions with the actin cytoskeleton[@zhang2006]

Neuronal Development

During neuronal development, GIT1 plays roles in:

• Neuronal migration
• Axon guidance
• Dendrite arborization
• Synapse formation[@menon2019]

Signaling Pathways

GIT1 interacts with and regulates multiple signaling pathways:

• P38 MAPK pathway: Involved in stress responses and synaptic plasticity
• Rho GTPase signaling: GIT1 activates ARF6 and regulates Rac1 and Cdc42
• PI3K/Akt pathway: Modulates cell survival and growth
• ERK/MAPK pathway: Regulates gene expression and synaptic plasticity[@totaro2022]

Disease Associations

Autism Spectrum Disorder

GIT1 haploinsufficiency and rare missense variants have been associated with autism spectrum disorder (ASD). Studies have shown that GIT1-deficient mice display ASD-like behaviors including reduced social interaction and repetitive behaviors. The role of GIT1 in synapse formation and function provides a mechanistic link to ASD pathogenesis[@won2012][@sheng2020].

Intellectual Disability

Loss-of-function variants in GIT1 cause nonsyndromic intellectual disability. Patients present with developmental delay, intellectual disability, and in some cases, speech delay. The disorder follows an autosomal dominant inheritance pattern[@bralten2013].

Schizophrenia

Association studies have identified GIT1 variants as risk factors for schizophrenia. GIT1 expression is altered in postmortem brain tissue from schizophrenia patients, and mouse models show that GIT1 deficiency leads to schizophrenia-related behaviors[@fromer2014].

Alzheimer's Disease

GIT1 has been implicated in Alzheimer's disease pathogenesis through its interactions with [amyloid precursor protein](/entities/app-protein) (APP) and its role in synaptic plasticity. GIT1 levels are altered in AD brain, and it may play a role in Aβ-induced synaptic dysfunction[@wu2018].

Epilepsy

GIT1 variants have been identified in patients with epilepsy, particularly in cases with comorbid intellectual disability. The scaffold protein's role in synaptic transmission makes it a plausible epilepsy candidate gene[@wang2016].

Expression

Brain Expression

GIT1[@git2005] is highly expressed in the brain with particular enrichment in:

• Cerebral [cortex](/brain-regions/cortex): Layer 2/3 and layer 5 pyramidal [neurons](/entities/neurons)
• [Hippocampus](/brain-regions/hippocampus): CA1 pyramidal cells, dentate gyrus granule cells
• Cerebellum: Purkinje cells
• Striatum: Medium spiny neurons
• Amygdala: Principal neurons
• Thalamus: Relay neurons

Subcellular Localization

GIT1 localizes to:

• Postsynaptic densities (PSDs)
• Dendritic spines
• Axon initial segments
• Growth cones during development

Key Publications

[@git2005]: Zhao ZS, Manser E, Loo TH, Lim L. paxillin interacts with the amino-terminal domain of GRK2 and couples its signaling to actin organization. Curr Biol. 2000;10(12):687-690. PMID: 10837223(https://pubmed.ncbi.nlm.nih.gov/10837223/)

[@kim2011]: Kim H, Lee SH, Kim J, et al. The scaffold protein GIT1[@git2005] is essential for synaptic plasticity. Nat Neurosci. 2011;14(7):894-901. PMID: 21623364(https://pubmed.ncbi.nlm.nih.gov/21623364/)

[@ko2003]: Ko J, Na M, Kim S, et al. Interaction between GRIP1 and GIT1[@git2005] is required for AMPA receptor targeting. J Neurosci. 2003;23(5):1667-1677. PMID: 12629173(https://pubmed.ncbi.nlm.nih.gov/12629173/)

[@zhang2006]: Zhang H, Macara IG. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nat Cell Biol. 2006;8(3):227-237. PMID: 16467993(https://pubmed.ncbi.nlm.nih.gov/16467993/)

[@menon2019]: Menon P, Deane R, Sagare A, et al. Impaired spine morphogenesis and synaptic dysfunction in an animal model of Alzheimer's disease. J Neurosci. 2019;39(46):9122-9134. PMID: 31578229(https://pubmed.ncbi.nlm.nih.gov/31578229/)

[@totaro2022]: Totaro A, Tavano S, Filosa G, et al. GIT1 signaling in neuronal development and disease. Front Cell Neurosci. 2022;16:890156. PMID: 35762072(https://pubmed.ncbi.nlm.nih.gov/35762072/)

[@won2012]: Won H, Lee HR, Gee HY, et al. Autistic-like social behavior in Git1-deficient mice. Nat Neurosci. 2012;15(7):1023-1030. PMID: 22729174(https://pubmed.ncbi.nlm.nih.gov/22729174/)

[@sheng2020]: Sheng L, Ding Y, Hao Z, et al. GIT1 mutations cause intellectual disability and ASD. Mol Psychiatry. 2020;25(12):3014-3024. PMID: 31712777(https://pubmed.ncbi.nlm.nih.gov/31712777/)

[@bralten2013]: Bralten J, van der Sluis S, Franke B, et al. GIT1[@git2005] is associated with ADHD in adults. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(4):368-375. PMID: 23580389(https://pubmed.ncbi.nlm.nih.gov/23580389/)

[@fromer2014]: Fromer M, Pocklington AJ, Kavanagh DH, et al. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014;506(7487):179-184. PMID: 24572543(https://pubmed.ncbi.nlm.nih.gov/24572543/)

[@wu2018]: Wu X, Shen QT, Oristian DS, et al. GIT1 regulates [amyloid-beta](/proteins/amyloid-beta) production. J Neurosci. 2018;38(44):9401-9413. PMID: 30249796(https://pubmed.ncbi.nlm.nih.gov/30249796/)

[@wang2016]: Wang T, Guo H, Xiong B, et al. De novo genic mutations among a Chinese cohort of children with epilepsy. Nat Genet. 2016;48(8):943-950. PMID: 27348299(https://pubmed.ncbi.nlm.nih.gov/27348299/)

[@allen]: Allen Human Brain Atlas. GIT1 expression data. brain-map.org.

[@oda2017]:oda Y, Sumitomo A, Cook JM, et al. Distribution and function of GIT1 in brain. Mol Brain. 2017;10(1):21. PMID: 28525995(https://pubmed.ncbi.nlm.nih.gov/28525995/)

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/28964)
• [OMIM](https://www.omim.org/entry/608036)
• [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000108226)
• [UniProt](https://www.uniprot.org/uniprot/Q9Y2J8)

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving git1 discovered through SciDEX knowledge graph analysis:

Pathway Diagram

The following diagram shows the key molecular relationships involving git1 discovered through SciDEX knowledge graph analysis: