MYO5B — Myosin Vb

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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>

Overview

...

MYO5B — Myosin Vb

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 actin

A 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 dynamics

Synaptic 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 sites

Interaction 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)

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)

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MYO5B — Myosin Vb

MYO5B — Myosin Vb

Overview

MYO5B — Myosin Vb

Overview

Gene Structure and Protein

Molecular Function

Motor Activity

Intracellular Transport

Cargo Adaptors

Tissue Expression

Epithelial Expression

Neuronal Expression

Disease Associations

Microvillus Inclusion Disease

Neurodegenerative Diseases

Parkinson's Disease

Alzheimer's Disease

Amyotrophic Lateral Sclerosis

Other Neurological Conditions

Mechanistic Connections

Axonal Transport

Synaptic Function

Connection to Neurodegeneration

Interaction Networks

Motor Protein Interactions

Cargo Adaptor Proteins

Pathway Membership

Therapeutic Implications

Drug Development

Biomarker Potential

Research Methods

Studying Myosin Vb

Key Publications

See Also

References

External Links