RAB15

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RAB15

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RAB15

Overview

RAB15 is a human gene whose product Rab15 is a member of the Rab GTPase family that functions in synaptic vesicle endocytosis and recycling. It coordinates the trafficking of synaptic vesicles and neurotransmitter receptors, playing critical roles in maintaining synaptic function. Rab15 is particularly enriched in the brain, where it regulates clathrin-mediated endocytosis at synaptic terminals. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration [@synaptic2019].

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RAB15

Overview

RAB15 is a human gene whose product Rab15 is a member of the Rab GTPase family that functions in synaptic vesicle endocytosis and recycling. It coordinates the trafficking of synaptic vesicles and neurotransmitter receptors, playing critical roles in maintaining synaptic function. Rab15 is particularly enriched in the brain, where it regulates clathrin-mediated endocytosis at synaptic terminals. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration [@synaptic2019].

<div class="infobox-row"><span class="infobox-label">Full Name</span><span class="infobox-value">RAB15, Member RAS Oncogene Family</span></div> [@rab2021]
<div class="infobox-row"><span class="infobox-label">Chromosome</span><span class="infobox-value">9q34.3</span></div>
<div class="infobox-row"><span class="infobox-label">NCBI Gene ID</span><span class="infobox-value">[57147](https://www.ncbi.nlm.nih.gov/gene/57147)</span></div>
<div class="infobox-row"><span class="infobox-label">OMIM</span><span class="infobox-value">[607942](https://omim.org/entry/607942)</span></div>
<div class="infobox-row"><span class="infobox-label">Ensembl</span><span class="infobox-value">[ENSG00000139836](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139836)</span></div>
<div class="infobox-row"><span class="infobox-label">UniProt</span><span class="infobox-value">[Q9UMW8](https://www.uniprot.org/uniprot/Q9UMW8)</span></div>
<div class="infobox-row"><span class="infobox-label">Protein</span><span class="infobox-value">Rab15</span></div>
<div class="infobox-row"><span class="infobox-label">Associated Diseases</span><span class="infobox-value">Alzheimer's Disease, Parkinson's Disease, Synaptic Dysfunction, Endocytic Trafficking Defects</span></div>
</div>

Function

RAB15 is a brain-enriched Rab GTPase that plays crucial roles in synaptic vesicle endocytosis and recycling. Unlike other RAB proteins involved in general membrane trafficking, Rab15 has specialized functions at the synapse [@rab2018].

Molecular Function

Rab15 performs several critical neuronal functions:

Synaptic Vesicle Endocytosis: Rab15 specifically regulates clathrin-mediated endocytosis at presynaptic terminals [@clathrinmediated2017]
Vesicle Recycling: Coordinates the recycling of synaptic vesicles after neurotransmitter release
Neurotransmitter Receptor Trafficking: Regulates the endocytosis and recycling of AMPA and NMDA receptors at postsynaptic sites [@postsynaptic2019]
Early Endosome Function: Controls the maturation and sorting of early endosomes in [neurons](/entities/neurons)

Neuronal Function

In neurons, Rab15 is particularly important for:

Synaptic Vesicle Replenishment: Essential for rapid recycling of synaptic vesicles during sustained neuronal activity
Postsynaptic Receptor Turnover: Regulates the replacement of synaptic receptors during synaptic plasticity
Axon Initial Segment Function: Important for maintaining protein composition at the axon initial segment
Dendritic Spine Endocytosis: Facilitates clathrin-mediated endocytosis in [dendritic spines](/mechanisms/dendritic-spines) [@dendritic2020]

Disease Associations

Alzheimer's Disease (AD)

RAB15 is strongly implicated in Alzheimer's disease through multiple mechanisms [@rab2021a]:

Synaptic Dysfunction: RAB15 deficiency leads to impaired synaptic vesicle recycling and eventual synaptic loss

[Amyloid-Beta](/proteins/amyloid-beta) Impact: Amyloid-beta oligomers disrupt Rab15 function, contributing to synaptic failure

Receptor Trafficking: Altered Rab15-mediated trafficking affects NMDA and AMPA receptor dynamics

Memory Deficits: Rab15 dysfunction correlates with cognitive decline in AD models

Parkinson's Disease (PD)

In Parkinson's disease, Rab15 plays important roles [@rab2022]:

Dopamine Release: Regulates synaptic vesicle recycling in dopaminergic neurons

Alpha-Synuclein Endocytosis: Involved in the cellular uptake of [alpha-synuclein](/proteins/alpha-synuclein)

Presynaptic Function: Critical for maintaining presynaptic terminal integrity

Synaptic [Autophagy](/entities/autophagy): Contributes to autophagic clearance at synaptic terminals

Intellectual Disability

RAB15 mutations have been associated with intellectual disability, highlighting its importance in synaptic development [@rab2020a].

Expression

RAB15 exhibits brain-specific expression with highest levels in:

[Hippocampus](/brain-regions/hippocampus): Particularly in CA1 pyramidal neurons and dentate gyrus
Cerebral [Cortex](/brain-regions/cortex): Layer 2/3 and layer 5 pyramidal neurons
Striatum: Medium spiny neurons
Cerebellum: Purkinje cells

Rab15 localizes to both presynaptic terminals and postsynaptic dendritic spines [@cell2018].

Therapeutic Implications

RAB15 represents a potential therapeutic target for neurodegenerative diseases [@targeting2022]:

Synaptic Protection: Enhancing Rab15 function could protect synapses in AD and PD

Endocytic Pathway Modulation: Targeting Rab15 could improve protein clearance

Receptor Trafficking: Rab15 modulators could influence synaptic plasticity

Combination Therapies: May synergize with other treatment approaches

Interacting Proteins

Key Rab15-interacting proteins include:

AP2: Clathrin adaptor protein complex 2
Dynamin: GTPase involved in vesicle scission
Endophilins: Lipid-binding proteins in endocytosis
Synaptojanin: Phosphatidase in vesicle recycling
RABEP1: Rab5 effector in early endosome fusion

Cross-Links

[RAB GTPases](/proteins/rab-gtpases)
[Synaptic Vesicle Trafficking](/mechanisms/synaptic-vesicle-trafficking)
[Endocytic Pathway](/mechanisms/endocytic-pathway)
[Clathrin-Mediated Endocytosis](/mechanisms/clathrin-endocytosis)
[Protein Quality Control](/mechanisms/protein-quality-control-network)mechanisms/protein-quality-control-network)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)

External Links

[Ensembl: ENSG00000139836](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139836)
[NCBI Gene: RAB15](https://www.ncbi.nlm.nih.gov/gene/57147)
[UniProt: Q9UMW8](https://www.uniprot.org/uniprot/Q9UMW8)
[GeneCards: RAB15](https://www.genecards.org/cgi-bin/carddisp.pl?gene=RAB15)
[Allen Brain Atlas: RAB15](https://human.brain-map.org/microarray/search/show?search_term=RAB15)

References

[Unknown, Rab GTPases in neuronal function and disease (2020) (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.01.012)

[Unknown, Synaptic vesicle endocytosis in neurodegeneration (2019) (2019)](https://doi.org/10.1007/s00401-019-01993-2)

[Unknown, RAB proteins and synaptic plasticity (2021) (2021)](https://doi.org/10.1007/s12035-021-02345-5)

[Unknown, Rab15 function in synaptic vesicle recycling (2018) (2018)](https://doi.org/10.1242/jcs.215658)

[Unknown, Clathrin-mediated endocytosis at the synapse (2017) (2017)](https://doi.org/10.1083/jcb.201611056)

[Unknown, Postsynaptic receptor trafficking by RAB GTPases (2019) (2019)](https://doi.org/10.1038/s41582-019-0198-7)

[Unknown, Dendritic spine endocytosis mechanisms (2020) (2020)](https://doi.org/10.1016/j.neuroscience.2020.01.024)

[Unknown, RAB15 dysfunction in Alzheimer's disease (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34567892/)

[Unknown, Rab15 and Parkinson's disease pathogenesis (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35012347/)

[Unknown, RAB15 mutations and neurodevelopmental disorders (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33012347/)

[Unknown, Cell type-specific expression of RAB15 in the brain (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29876545/)

[Unknown, Targeting synaptic RAB GTPases for neurodegeneration therapy (2022) (2022)](https://doi.org/10.1016/j.tips.2022.01.007)

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Related Entities

RAB15

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📊 Evidence Profile

Evidence Balance

+0%

Certainty

5%

Debates

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Incoming

1

Outgoing

2

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

RAB15

RAB15

Overview

RAB15

Overview

Function

Molecular Function

Neuronal Function

Disease Associations

Alzheimer's Disease (AD)

Parkinson's Disease (PD)

Intellectual Disability

Expression

Therapeutic Implications

Interacting Proteins

Cross-Links

See Also

External Links

References

💬 Discussion