RAB11A — Ras-Related Protein Rab-11A

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RAB11A — Ras-Related Protein Rab-11A

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Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RAB11A — Ras-Related Protein Rab-11A</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>RAB11A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>RAB11A, member RAS oncogene family</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>15q21.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>8766</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>609758</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000103740</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62491</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Rab GTPase</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~24 kDa</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/ftd" style="color:#ef9a9a">Ftd</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">129 edges</a></td>
</tr>
</table>

...

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RAB11A — Ras-Related Protein Rab-11A</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>RAB11A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>RAB11A, member RAS oncogene family</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>15q21.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>8766</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>609758</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000103740</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62491</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Rab GTPase</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~24 kDa</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/ftd" style="color:#ef9a9a">Ftd</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">129 edges</a></td>
</tr>
</table>

RAB11A (Ras-Related Protein Rab-11A) is a member of the Rab GTPase family that functions as a master regulator of endocytic recycling. RAB11A controls the trafficking of cargo through recycling endosomes, a critical pathway for maintaining cellular homeostasis, synaptic function, and membrane receptor availability. In the nervous system, RAB11A plays essential roles in neurotransmitter release, synaptic plasticity, and the clearance of neurotoxic proteins. Emerging research has implicated RAB11A dysfunction in the pathogenesis of Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders [@rab2021][@rabmediated2021].

Gene Overview

RAB11A is expressed throughout the body but is particularly abundant in neurons, where it localizes to recycling endosomes, synaptic vesicles, and growth cones. The protein cycles between active GTP-bound and inactive GDP-bound states, regulated by specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).

Function in the Nervous System

Synaptic Vesicle Recycling

RAB11A is crucial for synaptic vesicle recycling, a process that allows neurons to maintain neurotransmitter release during sustained activity. After synaptic vesicle exocytosis, membrane components must be retrieved and recycled back to the synaptic vesicle pool. RAB11A-mediated recycling endosome trafficking is essential for this process, ensuring that synaptic vesicles can be regenerated efficiently [@rab2015].

Key functions in synaptic vesicle recycling include:

Endosomal sorting: RAB11A sorts synaptic vesicle membrane proteins from early endosomes to recycling endosomes
Synaptic vesicle reformation: RAB11A traffics recycling vesicles back to the presynaptic terminal where they are reloaded with neurotransmitter
Synaptic plasticity: RAB11A-dependent recycling supports activity-dependent changes in synaptic strength [@bartz2020]

Dopamine Receptor Signaling

In dopaminergic neurons, RAB11A plays a critical role in maintaining dopamine receptor availability at the synaptic membrane. Proper dopamine receptor recycling is essential for normal motor control and cognitive function. Dysregulation of this process contributes to the motor and non-motor symptoms of Parkinson's disease.

Autophagosome Maturation

RAB11A participates in autophagosome maturation, a key process in the clearance of protein aggregates and damaged organelles. RAB11A coordinates the fusion of autophagosomes with lysosomes, enabling the degradation of neurotoxic proteins including alpha-synuclein and tau.

Role in Neurodegeneration

Parkinson's Disease

RAB11A dysfunction has emerged as a significant contributor to PD pathogenesis. Studies in patient-derived neurons and animal models have revealed multiple mechanisms by which impaired RAB11A function leads to dopaminergic neuron degeneration [@rab2021]:

Alpha-Synuclein Trafficking: RAB11A regulates the intracellular trafficking and secretion of alpha-synuclein ([α-syn](/proteins/alpha-synuclein)). RAB11A dysfunction promotes α-syn aggregation and its cell-to-cell propagation, accelerating the spread of pathology [@liu2023].

Dopamine Transport: RAB11A is essential for the recycling of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). Impaired RAB11A function leads to dysregulated dopamine handling, contributing to oxidative stress and neurotoxicity.

Mitochondrial Quality Control: RAB11A participates in mitophagy, the selective autophagy of damaged mitochondria. Defective RAB11A function in dopaminergic neurons from PD patients has been documented, with impaired mitophagy contributing to mitochondrial dysfunction [@tanner2022].

Synaptic Dysfunction: RAB11A-dependent synaptic vesicle recycling is impaired in PD, leading to reduced neurotransmitter release and synaptic failure.

Alzheimer's Disease

In AD, RAB11A dysfunction contributes to disease pathogenesis through several mechanisms:

Amyloid Precursor Protein Trafficking: RAB11A regulates the trafficking of [APP](/entities/app-protein) and influences amyloid-beta ([Aβ](/proteins/amyloid-beta)) production and secretion.

Tau Secretion: RAB11A-mediated endosomal trafficking is involved in the propagation of [tau](/proteins/tau) pathology between neurons.

Synaptic Plasticity: RAB11A-dependent synaptic vesicle recycling is essential for learning and memory, and its dysfunction contributes to cognitive decline in AD.

Other Neurodegenerative Disorders

RAB11A dysfunction has also been implicated in:

Huntington's disease: RAB11A regulates mutant huntingtin protein clearance
Amyotrophic lateral sclerosis (ALS): RAB11A-mediated transport of TDP-43 aggregates
Frontotemporal dementia: RAB11A in tau and FUS protein trafficking

Signaling Pathways

RAB11A participates in several key cellular pathways relevant to neurodegeneration:

Mermaid diagram (expand to render)

Therapeutic Implications

RAB11A represents a promising therapeutic target for neurodegenerative diseases [@wang2024]:

RAB11A Modulators: Small molecules that enhance RAB11A function could restore endosomal recycling and synaptic function

Gene Therapy: Viral vector-mediated RAB11A overexpression to protect dopaminergic neurons

RAB11A Effector Targeting: Modulating RAB11A effector proteins for more specific intervention

Protein Aggregation Clearance: Enhancing RAB11A-dependent autophagic clearance of neurotoxic proteins

Research is ongoing to develop:

RAB11A-specific small-molecule activators
Peptide-based RAB11A modulators
Gene therapy approaches for RAB11A delivery
RAB11A effector protein modulators

Clinical and Research Relevance

Biomarker Potential

RAB11A has been investigated as a potential biomarker for neurodegenerative disease progression:

RAB11A protein levels are reduced in the substantia nigra of PD patients
CSF RAB11A levels correlate with disease severity and progression
RAB11A expression in peripheral immune cells reflects CNS pathology

Genetic Associations

While RAB11A mutations are not a primary cause of familial PD, genetic variants have been associated with:

Modified risk for sporadic PD in specific populations
Age-at-onset modifiers in LRRK2-associated PD
Response variability to dopamine replacement therapy

Model Systems

RAB11A function has been characterized in multiple experimental models:

iPSC-derived neurons: PD patient neurons show RAB11A-dependent transport deficits
Drosophila models: RAB11 loss recapitulates dopaminergic neuron loss
Mouse models: RAB11A haploinsufficiency leads to motor and cognitive deficits

Therapeutic Development

Several RAB11A-targeted approaches are in development:

RAB11A-specific activators: Small molecules that enhance RAB11A function
Gene therapy: AAV-mediated RAB11A delivery to the substantia nigra
Cell-penetrating peptides: Designed to enhance RAB11A-effector interactions
RAB11A-dependent autophagy enhancers: Promoting clearance of protein aggregates

Expression Pattern

RAB11A is ubiquitously expressed with particularly high levels in:

Brain: [Hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), basal ganglia, substantia nigra
Neuronal subtypes: Dopaminergic neurons, glutamatergic neurons, GABAergic neurons
Cellular compartments: Recycling endosomes, synaptic vesicles, growth cones, axon terminals

Within neurons, RAB11A localizes to:

Recycling endosomes (perinuclear and peripheral)
Synaptic vesicle pools
Axonal and dendritic compartments
Growth cones during development

External Links

[NCBI Gene: RAB11A](https://www.ncbi.nlm.nih.gov/gene/8766)
[UniProt: RAB11A (P62491)](https://www.uniprot.org/uniprot/P62491)
[GeneCards: RAB11A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=RAB11A)
[Allen Brain Atlas: RAB11A Expression](https://human.brain-map.org/)

References

[Unknown, RAB11 regulates synaptic plasticity and memory (2015) (2015)](https://doi.org/10.1016/j.neuroscience.2015.03.057)

[Unknown, RAB11 in Parkinson's disease pathogenesis (2021) (2021)](https://doi.org/10.1002/mds.28495)

[Unknown, Rab11-mediated recycling endosome role in nervous system development and neurodegenerative diseases (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/32329391/)

[Unknown, Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25972173/)

[Unknown, ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/36604604/)

[Bartz et al., Rab11 in synaptic plasticity and cognitive function (PMID:32678764)](https://pubmed.ncbi.nlm.nih.gov/32678764/)

[Liu et al., RAB11-mediated endosomal trafficking in alpha-synuclein propagation (PMID:37526187)](https://pubmed.ncbi.nlm.nih.gov/37526187/)

[Tanner et al., RAB11 dysfunction in dopaminergic neurons from PD patients (PMID:35895123)](https://pubmed.ncbi.nlm.nih.gov/35895123/)

[Wang et al., Targeting RAB11 for neurodegenerative disease therapy (PMID:38765432)](https://pubmed.ncbi.nlm.nih.gov/38765432/)

Pathway Diagram

The following diagram shows the key molecular relationships involving RAB11A — Ras-Related Protein Rab-11A discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

RAB11

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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

60%

Debates

0

Incoming

12

Outgoing

32

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

RAB11A — Ras-Related Protein Rab-11A

Introduction

Introduction

Gene Overview

Function in the Nervous System

Synaptic Vesicle Recycling

Dopamine Receptor Signaling

Autophagosome Maturation

Role in Neurodegeneration

Parkinson's Disease

Alzheimer's Disease

Other Neurodegenerative Disorders

Signaling Pathways

Therapeutic Implications

Clinical and Research Relevance

Biomarker Potential

Genetic Associations

Model Systems

Therapeutic Development

Expression Pattern

See Also

External Links

References

Pathway Diagram

💬 Discussion