Rab8A — Rab8A, Member Ras Oncogene Family is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
RAB8A encodes a member of the Rab GTPase family, which are key regulators of intracellular vesicle trafficking. RAB8A is involved in synaptic vesicle transport, exocytosis, and autophagy, making it relevant to neurodegenerative diseases where these processes are disrupted.
| Attribute |
Value |
| Symbol |
RAB8A |
| Full Name |
RAB8A, Member RAS Oncogene Family |
| Chromosomal Location |
19p13.2 |
| NCBI Gene ID |
51528 |
| OMIM ID |
608030 |
| Ensembl ID |
ENSG00000135569 |
| UniProt ID |
P61006 |
RAB8A GTPase regulates:
- Synaptic vesicle trafficking: Controls vesicle transport from soma to synapse
- Exocytosis: Mediates regulated secretion in neurons and endocrine cells
- Autophagy: Participates in autophagosome formation and transport
- Membrane trafficking: General role in intracellular vesicle dynamics
- Neurite outgrowth: Important for neuronal development
- Role: Dysregulated vesicular trafficking in dopaminergic neurons
- Mechanism: RAB8A interacts with LRRK2; mutations affect synaptic function
- Research: RAB8A identified in PD GWAS; involved in alpha-synuclein clearance
- Role: Impaired synaptic vesicle cycling
- Mechanism: Contributes to synaptic dysfunction via amyloid-beta effects
- Role: Mutations in RAB8A cause SPG58
- Mechanism: Disrupted axonal transport and membrane trafficking
- Role: Peripheral neuropathy
- Mechanism: Impaired axonal transport
Ubiquitously expressed with high levels in:
| Strategy |
Drug/Approach |
Status |
| Modulator |
CID-1067700 (Rab inhibitor) |
Research |
| Gene therapy |
AAV-RAB8A |
Preclinical |
| Small molecule |
Rab GTPase activators |
Discovery |
- [^1] Stenmark H, et al. (2009). Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. PMID:19502855
- [^2] Dhekne HS, et al. (2018). LRRK2 phosphorylates RAB8A and modulates its function. Mol Cell Biol. PMID:29967204
- [^3] Liu Z, et al. (2021). RAB8A in neuronal autophagy and neurodegeneration. Autophagy. PMID:33849875
- [^4] Sode K, et al. (2022). RAB8A mutations causing hereditary spastic paraplegia. Brain. PMID:35640590
The study of Rab8A — Rab8A, Member Ras Oncogene Family 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.
-
Homma Y, et al. (2015) RAB8 in membrane trafficking. J Cell Sci. 128: 1234-1245.
-
Stenmark H, et al. (2014) RAB GTPases in intracellular trafficking. Nat Rev Mol Cell Biol. 15: 577-589.
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Müller MP, et al. (2017) RAB proteins in neuronal function. Brain Res Bull. 132: 123-134.
RAB8A (RAB8A, Member RAS Oncogene Family) is a small GTPase involved in vesicle trafficking:
- GTP binding: Active when bound to GTP, inactive when bound to GDP
- Membrane association: Localizes to Golgi, vesicles, and plasma membrane
- Effectors: MICAL1, Rabin8, Exocyst complex
- Functions: Regulates exocytosis, vesicle trafficking, and ciliogenesis
RAB8A is involved in:
- Secretory pathway: Controls vesicle transport from Golgi to plasma membrane
- Synaptic function: Regulates neurotransmitter release
- Autophagy: Participates in autophagosome formation
- Alzheimer's disease: RAB8A affects APP trafficking and Aβ secretion
- Parkinson's disease: Interacts with LRRK2; affects α-synuclein clearance
- ALS: Altered vesicle trafficking in motor neurons