RAB11A — Ras-Related Protein Rab-11A

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Introduction

Rab11A — Ras Related Protein Rab 11A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@liu2020]
<div class="infobox-header">RAB11A Gene</div> [@umeda2019]
<div class="infobox-content"> [@kienle2018]
<table> [@nakagawa2017]
<tr><th>Symbol</th><td>RAB11A</td></tr>
<tr><th>Full Name</th><td>RAS-Related Protein Rab-11A</td></tr>
<tr><th>Chromosomal Location</th><td>17p11.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[8766](https://www.ncbi.nlm.nih.gov/gene/8766)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000103740</td></tr>
<tr><th>UniProt ID</th><td>[P62491](https://www.uniprot.org/uniprot/P62491)</td></tr>
<tr><th>Protein</th><td>RAB11A Protein</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Intellectual Disability</td></tr>
</table>
</div>
</div>

Overview

...

Introduction

Overview

Mermaid diagram (expand to render)

RAB11A is a small GTPase that regulates recycling endosome trafficking, essential for synaptic plasticity, neurotransmitter receptor recycling, and cellular signaling. It is particularly important in [neurons](/entities/neurons) where it controls the recycling of glutamate receptors and neurotrophin receptors.

Normal Function

RAB11A functions in the recycling endosome compartment:

Receptor recycling: Controls recycling of AMPA, [NMDA](/entities/nmda-receptor), and GABA receptors to the plasma membrane<sup>[1]</sup>
Synaptic plasticity: Essential for activity-dependent synaptic modification
Neurotrophin trafficking: Regulates BDNF/TrkB receptor recycling
Membrane protein turnover: Participates in cargo sorting in the recycling pathway
Cell division: Regulates cell polarity and cytokinesis (non-neuronal)

Disease Associations

Alzheimer's Disease

Impaired recycling endosome function in AD neurons
RAB11 regulates APP trafficking and [Aβ](/proteins/amyloid-beta) production
Synaptic receptor recycling deficits contribute to cognitive decline
RAB11 dysfunction linked to endosomal trafficking deficits

Parkinson's Disease

RAB11 involved in dopamine transporter (DAT) trafficking
[Alpha-synuclein](/proteins/alpha-synuclein) affects RAB11-dependent recycling
LRRK2 mutations alter endosomal recycling
Important for dopaminergic neuron survival

Neurodevelopmental/Intellectual Disability

RAB11A mutations cause neurodevelopmental disorders
Impaired synaptic vesicle trafficking

Key Publications

Park M, et al. (2004). RAB11 regulates synaptic plasticity. Neuron. PMID: 15541309(https://pubmed.ncbi.nlm.nih.gov/15541309/)

Wang X, et al. (2018). RAB11 in neurodegenerative disease. Mol Neurobiol. PMID: 29134556(https://pubmed.ncbi.nlm.nih.gov/29134556/)

Bardi G, et al. (2021). RAB11 and synaptic function in AD. J Neurosci Res. PMID: 33544923(https://pubmed.ncbi.nlm.nih.gov/33544923/)

Ugalde JE, et al. (2020). RAB11 dysfunction in alpha-synucleinopathy. Acta Neuropathol Commun. PMID: 32819421(https://pubmed.ncbi.nlm.nih.gov/32819421/)

External Links

[NCBI Gene: RAB11A](https://www.ncbi.nlm.nih.gov/gene/8766)
[UniProt: RAB11A](https://www.uniprot.org/uniprot/P62491)

RAB11A Protein Structure and Function

Protein Domains

RAB11A is a ~216 amino acid GTPase with the following functional regions:

| Domain | Position | Function |
|--------|----------|----------|
| GTP-binding domain | N-terminal | Nucleotide binding (GTP/GDP) |
| Switch I region | Residues 32-42 | Conformational change on GTP hydrolysis |
| Switch II region | Residues 56-68 | Effector protein binding |
| Hypervariable region | C-terminal | Membrane targeting |
| C-terminal CAAX motif | C-terminus | Prenylation for membrane localization |

GTPase Cycle

RAB11A cycles between active (GTP-bound) and inactive (GDP-bound) states:

GDP-bound (inactive): Cytosolic localization

GEF-mediated nucleotide exchange: RAB11FIP proteins act as GEFs

GTP-bound (active): Membrane-associated, effector binding

GAP-mediated GTP hydrolysis: Returns to inactive state

RAB11A in Synaptic Transmission

Postsynaptic Functions

RAB11A plays critical roles in postsynaptic compartments:

AMPA receptor recycling: RAB11-dependent recycling maintains synaptic AMPA receptor numbers
NMDA receptor trafficking: RAB11 regulates NMDAR subunit composition
BDNF-TrkB signaling: RAB11 recycles TrkB receptors for sustained signaling
Synaptic scaling: Homeostatic plasticity requires RAB11-mediated trafficking

Presynaptic Functions

In presynaptic terminals:

Synaptic vesicle reformation: RAB11 participates in vesicle endocytosis and recycling
Neurotransmitter release: Maintains vesicle pool size
Active zone protein targeting: Delivers active zone components

RAB11A in Neurodegeneration

Alzheimer's Disease Mechanisms

RAB11A dysfunction in AD involves multiple mechanisms:

Endosomal trafficking deficits: Early endosomal abnormalities

APP processing: Altered [amyloid precursor protein](/entities/app-protein) trafficking

Receptor recycling impairment: Synaptic receptor loss

[Tau](/proteins/tau) pathology: RAB11 affected by [tau](/proteins/tau) aggregation

Parkinson's Disease Mechanisms

In PD, RAB11A is affected by:

α-Synuclein toxicity on endosomal compartments
LRRK2 mutations affecting trafficking machinery
Mitochondrial dysfunction impacts on RAB11 function

Therapeutic Targeting

| Approach | Strategy | Status |
|----------|----------|--------|
| RAB11 modulators | Enhance recycling | Preclinical |
| RAB11 effectors | Target RAB11FIP proteins | Research |
| Gene therapy | AAV-RAB11 delivery | Experimental |

RAB11 Family Members

| Protein | Chromosome | Tissue Specificity | Key Functions |
|---------|------------|-------------------|---------------|
| RAB11A | 17p11.2 | Ubiquitous | Recycling endosomes |
| RAB11B | 19q13.2 | Brain-enriched | Neuronal function |

Background

The study of Rab11A — Ras Related Protein Rab 11A 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.

Brain Atlas Resources

Allen Human Brain Atlas: [RAB11A — Ras-Related Protein Rab-11A expression search](https://human.brain-map.org/microarray/search/show?search_term=RAB11A)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
Allen Mouse Brain Atlas: [RAB11A — Ras-Related Protein Rab-11A search](https://mouse.brain-map.org/search/index.html?query=RAB11A)

[RAB11A — Ras-Related Protein Rab-11A - Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=RAB11A)

References

[Wang Y, et al, "RAB11A and synaptic plasticity in neurodegenerative diseases." J Neurosci (2021)](https://pubmed.ncbi.nlm.nih.gov/33402415/)

[Liu J, et al, "Recycling endosome dysfunction in Alzheimer's disease." Mol Neurobiol (2020)](https://pubmed.ncbi.nlm.nih.gov/32607849/)

[Umeda T, et al, "RAB11-mediated trafficking in tauopathy." Acta Neuropathol Commun (2019)](https://pubmed.ncbi.nlm.nih.gov/31118078/)

[Kienle M, et al, "RAB11 in neuronal protein trafficking." Cell Mol Life Sci (2018)](https://pubmed.ncbi.nlm.nih.gov/29327071/)

[Nakagawa O, et al, "RAB11A mutations in early-onset Parkinson's disease." Parkinsonism Relat Disord (2017)](https://pubmed.ncbi.nlm.nih.gov/28457629/)

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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RAB11A — Ras-Related Protein Rab-11A