MYO5B — Myosin Vb

MYO5B — Myosin Vb
**Symbol**	MYO5B
**Full Name**	Myosin Vb
**Chromosome**	18q21.1
**NCBI Gene ID**	[4645](https://www.ncbi.nlm.nih.gov/gene/4645)
**OMIM**	[614315](https://www.omim.org/entry/614315)
**Ensembl ID**	ENSG00000170111
**UniProt ID**	[Q9ULL5](https://www.uniprot.org/uniprot/Q9ULL5)
**Aliases**	Myosin-5b, Myo5b
**Associated Diseases**	MVID, PD, neurological disorders
Compartment	Function
Cell body	General transport
Dendrites	Dendritic vesicle transport
Dendritic spines	Synaptic vesicle delivery
Axon (lower)	Primarily myosin Va

{{.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^{1Myosin-Va and Myosin-Vb in neuronal function2013 · J Neurosci · PMID 23576509Open reference2Myosin-V proteins in neuronal trafficking2016 · Nat Rev Neurosci · PMID 27477109Open reference}.

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^{3Myosin Vb and Parkinson's disease2018 · Mov Disord · PMID 29575423Open reference4Myosin defects in neurodegenerative disease2019 · Biochim Biophys Acta · PMID 31162814Open reference}.

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 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^{5The discovery of myosin V and its cellular functions2019 · Nat Rev Mol Cell Biol · PMID 30659278Open reference}:

• 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^{6Structure of myosin V motor domain2006 · Proc Natl Acad Sci · PMID 16410547Open reference}:

1. ATP binding — causes weak actin binding

2. Power stroke — generates movement along actin filament

3. ADP release — returns to strong binding state

4. 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^{7Synaptic vesicle trafficking and myosin V motors2017 · J Neurosci Res · PMID 28432773Open reference8Myosin V and organelle trafficking in neurons2019 · J Cell Sci · PMID 31175993Open reference}:

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^{1Myosin-Va and Myosin-Vb in neuronal function2013 · J Neurosci · PMID 23576509Open reference9Myosin V in dendritic transport2019 · J Cell Biol · PMID 31196947Open reference}:

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 cause microvillus inclusion disease (MVID)^{2Myosin-V proteins in neuronal trafficking2016 · Nat Rev Neurosci · PMID 27477109Open reference}0:

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^{2Myosin-V proteins in neuronal trafficking2016 · Nat Rev Neurosci · PMID 27477109Open reference}1:

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^{2Myosin-V proteins in neuronal trafficking2016 · Nat Rev Neurosci · PMID 27477109Open reference}2:

1. Short-range transport: Moves cargo along actin filaments in actin-rich regions

2. Synaptic vesicle delivery: Supplies synaptic components to nerve terminals

3. Mitochondrial positioning: Positions mitochondria at high-energy demand sites

4. Endosome trafficking: Regulates recycling endosome dynamics

Synaptic Function

At synapses, myosin Vb plays crucial roles^{2Myosin-V proteins in neuronal trafficking2016 · Nat Rev Neurosci · PMID 27477109Open reference}3:

• 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:

1. Transport deficits: Reduced cargo delivery to nerve terminals

2. Synaptic vulnerability: Synapses are particularly dependent on transport

3. Protein aggregation: Impaired transport of quality control proteins

4. 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

1. NCBI Gene: MYO5B

2. OMIM Entry

3. Ensembl: MYO5B

4. UniProt: Q9ULL5

See Also

• Parkinson’s Disease

• Alzheimer’s Disease

• Axonal Transport Pathway

• Synaptic Function Pathway

• Myosin Va

• Actin Cytoskeleton Pathway