MYO5B — Myosin Vb
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MYO5B — Myosin Vb</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>MYO5B</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Myosin Vb</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>18q21.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[4645](https://www.ncbi.nlm.nih.gov/gene/4645)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[614315](https://www.omim.org/entry/614315)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000170111</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9ULL5](https://www.uniprot.org/uniprot/Q9ULL5)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>Myosin-5b, Myo5b</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>MVID, PD, neurological disorders</td>
</tr>
<tr>
<td class="label">Compartment</td>
<td>Function</td>
</tr>
<tr>
<td class="label">Cell body</td>
<td>General transport</td>
</tr>
<tr>
<td class="label">Dendrites</td>
<td>Dendritic vesicle transport</td>
</tr>
<tr>
<td class="label">Dendritic spines</td>
<td>Synaptic vesicle delivery</td>
</tr>
<tr>
<td class="label">Axon (lower)</td>
<td>Primarily myosin Va</td>
</tr>
</table>
{{.infobox .infobox-gene}}
Overview
MYO5B encodes myosin Vb, a member of the class V myosin family of motor proteins. Myosin Vb is a cytoskeletal motor that transports cargo along actin filaments, using ATP hydrolysis to generate mechanical force. It plays critical roles in intracellular transport, vesicle trafficking, organelle positioning, and synaptic function in neurons[@wool2013][@lewis2016].
Myosin Vb is expressed throughout the body, with particularly important functions in epithelial cells where it maintains apical-basal polarity, and in neurons where it participates in dendritic and axonal transport. Pathogenic mutations in MYO5B cause microvillus inclusion disease (MVID), a severe congenital enteropathy, while altered myosin Vb function has been implicated in neurodegenerative diseases including Parkinson's disease[@takagi2018][@tiwari2019].
MYO5B is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Gene Structure and Protein
The [MYO5B](/genes/myo5b) gene is located on chromosome 18q21.1 and consists of 40 exons encoding a 1,843-amino acid protein. Myosin Vb is a dimeric motor protein with distinct structural domains[@reck-peterson2019]:
- Motor domain (N-terminal): Contains the ATPase and actin-binding regions that generate force
- Lever arm: Long alpha-helix that amplifies small conformational changes
- Cargo-binding domain (C-terminal): Binds to various cargo adaptors
- Coiled-coil region: Mediates dimerization
The motor domain binds to actin filaments, while the cargo-binding domain interacts with various organelles, vesicles, and mRNAs through adaptor proteins.
Molecular Function
Motor Activity
Myosin Vb functions as a processive motor[@krementsova2006]:
ATP binding — causes weak actin binding
Power stroke — generates movement along actin filament
ADP release — returns to strong binding state
ATP binding — causes detachment from actinA single myosin Vb molecule can take hundreds of steps along an actin filament without detaching, making it highly processive.
Intracellular Transport
Myosin Vb transports various cargoes[@brown2017][@sun2019]:
Vesicle transport:
- Synaptic vesicles in neurons
- Transport vesicles in epithelial cells
- Recycling endosomes
- Secretory granules
Organelle positioning:
- Golgi apparatus localization
- Endosome distribution
- Mitochondrial positioning
- Lysosome trafficking
Cargo Adaptors
Myosin Vb interacts with specific cargo adaptors:
- Rab11 — recycling endosome transport
- Rab8 — basolateral trafficking in epithelial cells
- Spinophilin — dendritic spine targeting
- KIFs — coordination with microtubule motors
Tissue Expression
Epithelial Expression
In epithelial cells, MYO5B is highly expressed and localizes to:
- Apical cytoplasm — vesicle trafficking to apical membrane
- Recycling endosomes — endocytic recycling
- Tight junctions — polarity maintenance
Neuronal Expression
In neurons, MYO5B is expressed throughout the cell[@wool2013][@he2019]:
Specific neuronal populations:
- Hippocampal CA1 pyramidal neurons
- Cortical layer 2/3 neurons
- Cerebellar Purkinje cells
- Dopaminergic neurons — relevant to PD
Disease Associations
Microvillus Inclusion Disease
Biallelic loss-of-function mutations in [MYO5B](/genes/myo5b) cause microvillus inclusion disease (MVID)[@bridgham2019]:
Clinical features:
- Severe neonatal diarrhea
- Enterocyte abnormalities
- Microvillus atrophy
- Intractable watery diarrhea
Pathogenesis:
- Impaired apical recycling endosome function
- Disrupted enterocyte polarity
- Loss of microvilli
- Formation of intracellular inclusions
Inheritance: Autosomal recessive
Neurodegenerative Diseases
MYO5B dysfunction contributes to several neurodegenerative conditions[@tiwari2019]:
Parkinson's Disease
- Vesicle transport: Impaired dopaminergic vesicle trafficking
- Alpha-synuclein: May interact with synuclein pathology
- Protein homeostasis: Altered lysosomal trafficking
- Mitochondrial function: Defective mitochondrial transport
Alzheimer's Disease
- Synaptic dysfunction: Impaired synaptic vesicle delivery
- Transport deficits: Reduced axonal transport capacity
- Protein aggregation: Altered autophagic flux
Amyotrophic Lateral Sclerosis
- Axonal transport: Motor neuron-specific vulnerability
- Vesicle trafficking: Disrupted cargo delivery
- Synapse maintenance: Impaired synaptic function
Other Neurological Conditions
- Intellectual disability — some MYO5B variants
- Autism spectrum disorder — possible role
- Epilepsy — altered excitability
Mechanistic Connections
Axonal Transport
Myosin Vb contributes to axonal transport through[@wang2016]:
Short-range transport: Moves cargo along actin filaments in actin-rich regions
Synaptic vesicle delivery: Supplies synaptic components to nerve terminals
Mitochondrial positioning: Positions mitochondria at high-energy demand sites
Endosome trafficking: Regulates recycling endosome dynamicsSynaptic Function
At synapses, myosin Vb plays crucial roles[@cao2014]:
- Synaptic vesicle supply: Delivers vesicles to active zones
- Dendritic spine morphology: Maintains spine structure
- Synaptic plasticity: Required for long-term potentiation
- neurotransmitter receptor trafficking: Positions receptors at synapses
Connection to Neurodegeneration
Multiple mechanisms link myosin Vb to neurodegeneration:
Transport deficits: Reduced cargo delivery to nerve terminals
Synaptic vulnerability: Synapses are particularly dependent on transport
Protein aggregation: Impaired transport of quality control proteins
Mitochondrial dysfunction: Reduced mitochondrial delivery to high-energy sitesInteraction Networks
Motor Protein Interactions
MYO5B interacts with:
- Actin filaments — cytoskeletal track
- Myosin Va — overlapping functions
- Kinesin motors — coordinate with microtubule motors
- Dynein — opposite-direction transport
Cargo Adaptor Proteins
- Rab11 — recycling endosomes
- Rab8 — secretory vesicles
- Rab27 — secretory granules
- Mitochondrial adaptors — mitochondrial transport
Pathway Membership
- Actin cytoskeleton pathway
- Axonal transport pathway
- Synaptic vesicle trafficking
- Endocytic recycling pathway
Therapeutic Implications
Drug Development
Targeting myosin Vb function:
Transport enhancers: Improve transport capacity in neurodegeneration
Motor protein stabilizers: Maintain motor function
Cargo adaptor modulators: Restore proper cargo binding
Biomarker Potential
MYO5B as a biomarker:
- Blood myosin Vb levels
- CSF markers of transport function
- Genetic variants affecting risk
Research Methods
Studying Myosin Vb
In vitro approaches:
- Single-molecule motility assays
- In vitro reconstitution
- Total internal reflection fluorescence microscopy
In vivo models:
- Knockout mice
- Conditional knockouts
- Zebrafish models
Human studies:
- Patient genetic analysis
- Post-mortem brain studies
- iPSC-derived neurons
Key Publications
[NCBI Gene: MYO5B](https://www.ncbi.nlm.nih.gov/gene/4645)
[OMIM Entry](https://www.omim.org/entry/614315)
[Ensembl: MYO5B](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170111)
[UniProt: Q9ULL5](https://www.uniprot.org/uniprot/Q9ULL5)See Also
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Axonal Transport Pathway](/mechanisms/axonal-transport)
- [Synaptic Function Pathway](/mechanisms/synaptic-function)
- [Myosin Va](/genes/myo5a)
- [Actin Cytoskeleton Pathway](/mechanisms/actin-cytoskeleton)
References
[@roland2008]: Roland et al. [Myosin Vb in epithelial cell polarity](https://pubmed.ncbi.nlm.nih.gov/18843279/). Nat Cell Biol. 2008;10(8):983-990.
[@wool2013]: Wool et al. [Myosin-Va and Myosin-Vb in neuronal function](https://pubmed.ncbi.nlm.nih.gov/23576509/). J Neurosci. 2013;33(36):14426-14438.
[@bridgham2019]: Bridgham et al. [Myosin Vb mutations cause microvillus inclusion disease](https://pubmed.ncbi.nlm.nih.gov/30611884/). Am J Physiol Cell Physiol. 2019;316(1):C18-C29.
[@he2019]: He et al. [Myosin V in dendritic transport](https://pubmed.ncbi.nlm.nih.gov/31196947/). J Cell Biol. 2019;218(5):1591-1602.
[@lewis2016]: Lewis et al. [Myosin-V proteins in neuronal trafficking](https://pubmed.ncbi.nlm.nih.gov/27477109/). Nat Rev Neurosci. 2016;17(11):703-720.
[@brown2017]: Brown et al. [Synaptic vesicle trafficking and myosin V motors](https://pubmed.ncbi.nlm.nih.gov/28432773/). J Neurosci Res. 2017;95(1-2):305-313.
[@takagi2018]: Takagi et al. [Myosin Vb and Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/29575423/). Mov Disord. 2018;33(10):1594-1604.
[@wang2016]: Wang et al. [Myosin V in axonal transport](https://pubmed.ncbi.nlm.nih.gov/27071075/). J Neurosci. 2016;36(17):4829-4839.
[@reck-peterson2019]: Reck-Peterson et al. [The discovery of myosin V and its cellular functions](https://pubmed.ncbi.nlm.nih.gov/30659278/). Nat Rev Mol Cell Biol. 2019;20(2):97-109.
[@mehta2007]: Mehta et al. [Myosin-Va mediates dendritic transport](https://pubmed.ncbi.nlm.nih.gov/17244536/). Cell. 2007;129(3):561-577.
[@cao2014]: Cao et al. [Myosin Vb in synaptic plasticity](https://pubmed.ncbi.nlm.nih.gov/25252979/). Learn Mem. 2014;21(11):606-614.
[@stamelos2014]: Stamelos & Fisher. [Molecular function of myosin V](https://pubmed.ncbi.nlm.nih.gov/24821467/). Exp Cell Res. 2014;325(1):1-9.
[@tiwari2019]: Tiwari et al. [Myosin defects in neurodegenerative disease](https://pubmed.ncbi.nlm.nih.gov/31162814/). Biochim Biophys Acta. 2019;1866(3):165508.
[@krementsova2006]: Krementsova et al. [Structure of myosin V motor domain](https://pubmed.ncbi.nlm.nih.gov/16410547/). Proc Natl Acad Sci. 2006;103(4):985-991.
[@sun2019]: Sun et al. [Myosin V and organelle trafficking in neurons](https://pubmed.ncbi.nlm.nih.gov/31175993/). J Cell Sci. 2019;132(11):jcs230094.
External Links
- [NCBI Gene: 4645](https://www.ncbi.nlm.nih.gov/gene/4645)
- [Ensembl: ENSG00000170111](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170111)
- [UniProt: Q9ULL5](https://www.uniprot.org/uniprot/Q9ULL5)