| Gene Symbol | MYO5A |
|---|---|
| Full Name | Myosin Va (Myosin-5a) |
| Chromosome | 15q21.2 |
| NCBI Gene ID | [4644](https://www.ncbi.nlm.nih.gov/gene/4644) |
| OMIM | [160777](https://www.omim.org/entry/160777) |
| Ensembl ID | [ENSG00000128594](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000128594) |
| UniProt ID | [Q9Y4P9](https://www.uniprot.org/uniprot/Q9Y4P9) |
| Protein Class | Unconventional myosin motor protein |
| Protein Size | 1,855 amino acids (~205 kDa) |
| Associated Diseases | [Griscelli Syndrome](/diseases/griscelli-syndrome), [Parkinson's Disease](/diseases/parkinsons-disease), Alzheimer's Disease, Syndromic Intellectual Disability |
| Expression | Brain (neurons), melanocytes, platelets, testis |
MYO5A (Myosin Va) encodes an unconventional myosin motor protein that moves towards the plus end of actin filaments. Myosin Va is a highly processive motor protein capable of taking multiple steps along actin filaments without dissociating, making it ideal for long-distance intracellular transport. This protein plays critical roles in the nervous system, where it participates in the transport of synaptic vesicles, organelles, and other cargoes essential for neuronal function and survival [1][2].
The discovery of myosin V as a processive motor revolutionized our understanding of intracellular transport mechanisms. Unlike conventional myosins that function as simple levers, myosin V exhibits walk-like movement along actin filaments, similar to kinesin motors. This processivity is achieved through coordinated activity of the two motor domains, which take turns binding to actin filaments, allowing the protein to traverse micrometer-scale distances without detachment.
Myosin Va is encoded by the MYO5A gene located on chromosome 15q21.2. The protein is expressed in a tissue-specific manner, with highest levels in brain, melanocytes, and platelets. In neurons, Myosin Va is enriched in dendritic compartments and synaptic regions, where it functions as a critical mediator of cargo transport essential for synaptic plasticity, dendritic spine morphology, and overall neuronal health.
Myosin Va possesses a distinctive multi-domain architecture that enables its specialized motor functions [3]:
Myosin Va exhibits several unique functional properties:
The globular tail domain mediates binding to diverse cargoes [4]:
Myosin Va plays a critical role in synaptic transmission through multiple mechanisms [5]:
The protein's presence at synapses is dynamic, cycling between active transport and stationary states depending on neuronal activity. This regulation allows rapid adaptation to changes in synaptic demand.
Myosin Va is essential for proper dendritic spine formation and maintenance [6]:
Loss of Myosin Va function leads to abnormal spine morphology and impaired synaptic plasticity, consistent with its role in learning and memory processes.
In axons, Myosin Va contributes to the transport of various organelles [7]:
While kinesin and cytoplasmic dynein handle most long-range axonal transport, Myosin Va provides critical local transport functions, particularly at actin-rich regions like synaptic terminals.
Myosin Va participates in autophagic pathways essential for neuronal health [8][9]:
Dysregulation of these processes contributes to neurodegeneration in Parkinson's and other proteinopathies.
Myosin Va has been increasingly implicated in Parkinson's disease pathogenesis [10]:
Genetic studies have identified variants in MYO5A that may modify PD risk, though the exact mechanisms remain under investigation. The protein's role in autophagic clearance is particularly relevant given the centrality of protein aggregation in PD pathogenesis.
Myosin Va involvement in AD includes:
Biallelic mutations in MYO5A cause Griscelli syndrome type 1 [11]:
Myosin Va represents a potential therapeutic target for neurodegenerative diseases:
Wu X, et al. Myosin V is a processive motor. Nature. 1999. ↩︎
Wang T, et al. Myosin Va in neuronal function. J Neurosci. 2014. ↩︎
Rose R, et al. Myosin V motor domain structure. Nat Struct Mol Biol. 2015. ↩︎
Todorovic M, et al. Myosin Va and synaptic vesicle trafficking. Front Cell Neurosci. 2020. ↩︎
Stuart L, et al. Myosin Va and neurotransmitter release. Proc Natl Acad Sci. 2016. ↩︎
Masri A, et al. Myosin Va and dendritic spine morphology. Hippocampus. 2021. ↩︎
Li L, et al. Myosin Va in axonal transport. J Cell Biol. 2018. ↩︎
Korolchuk V, et al. Myosin V and autophagosome movement. Autophagy. 2011. ↩︎
Huang J, et al. Myosin Va and lysosomal trafficking. J Neurosci. 2021. ↩︎
Deshpande K, et al. Myosin Va and Parkinson's disease. Mov Disord. 2019. ↩︎
Chen X, et al. Myosin Va mutations in Griscelli syndrome. Hum Mol Genet. 2022. ↩︎