| Full Name | Myosin XVB |
| Gene Symbol | MYO15B |
| Chromosomal Location | 17p13.2 |
| NCBI Gene ID | [80177](https://www.ncbi.nlm.nih.gov/gene/80177) |
| OMIM | [607416](https://omim.org/entry/607416) |
| Ensembl | [ENSG00000167653](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000167653) |
| UniProt | [Q9UKS7](https://www.uniprot.org/uniprot/Q9UKS7) |
| Protein | Unconventional myosin XVB |
| Associated Diseases | Hearing loss, [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), neuropsychiatric disorders |
MYO15B encodes an unconventional myosin belonging to the myosin XV family. Myosins are motor proteins that use ATP hydrolysis to move along actin filaments, transporting cargoes and generating force. Unlike conventional myosins (such as myosin II in muscle), unconventional myosins perform diverse cellular functions including organelle transport, membrane trafficking, and cytoskeletal organization. MYO15B is expressed in various tissues including the brain and inner ear, where it participates in cellular processes relevant to neuronal function, hearing, and potentially neurodegenerative disease pathogenesis. The protein shares structural and functional features with MYO15A, another myosin XV family member crucial for hearing, though MYO15B has distinct expression patterns and functions. MYO15B contains the characteristic motor domain, neck region with IQ motifs for light chain binding, and a tail region involved in cargo binding and dimerization. The motor domain hydrolyzes ATP and interacts with actin filaments, while the tail domain determines cargo specificity and cellular localization. MYO15B functions as a dimer, with two motor domains working cooperatively to move along actin filaments, enabling processive movement similar to other class V myosins. This motor protein participates in intracellular transport, cytoskeletal dynamics, and potentially in synaptic function, with emerging evidence linking myosin dysfunction to neurodegenerative diseases. This page covers MYO15B's normal function, disease associations, expression patterns, and therapeutic implications for neurodegenerative conditions. [1][2]
MYO15B contains several functional domains characteristic of class V myosins:[3]
Motor Domain (N-terminal): The N-terminal motor domain (~700 amino acids) contains the ATP-binding pocket and actin-binding interface. This domain binds ATP and hydrolyzes it to generate force for movement along actin filaments. The motor domain includes conserved motifs for nucleotide binding (P-loop, Switch I, Switch II) that undergo conformational changes during the ATP hydrolysis cycle.
Neck Region (IQ Motifs): Following the motor domain, MYO15B contains multiple IQ motifs (Isoleucine-Glutamine) that serve as binding sites for calmodulin and calmodulin-like light chains. The neck region acts as a lever arm, amplifying small conformational changes in the motor domain into larger movements. The number and arrangement of IQ motifs influence the step size and processivity of the myosin.
Coiled-Coil Domain: The central region contains a coiled-coil domain that mediates dimerization. Dimerization is essential for processive movement, as the two motor domains can alternately bind to actin filaments, allowing the myosin to take steps along the filament without dissociating.
Cargo-Binding Tail (C-terminal): The C-terminal tail domain contains specific motifs for cargo binding. This region determines the specific cellular cargoes that MYO15B transports, including organelles, vesicles, proteins, and mRNAs.
MYO15B operates through a well-characterized myosin mechanochemical cycle:[4]
ATP Binding: The motor domain binds ATP, which induces detachment from actin filaments.
ATP Hydrolysis: ATP is hydrolyzed to ADP and Pi, storing energy in the motor domain.
Power Stroke: The release of Pi triggers a conformational change that generates force and moves the myosin along the actin filament.
ADP Release: ADP release resets the motor domain for another cycle.
New ATP Binding: New ATP binding completes the cycle and allows detachment.
The processive nature of MYO15B means it can take multiple steps along actin filaments without dissociating, making it ideal for long-distance transport.
MYO15B participates in intracellular transport:[5]
Vesicle Transport: MYO15B transports vesicles along actin filaments to their destinations within the cell.
Organelle Positioning: MYO15B helps position organelles including endosomes, Golgi-derived vesicles, and mitochondria.
Protein Trafficking: MYO15B carries specific proteins to their functional locations.
mRNA Transport: Some myosins transport mRNAs; MYO15B may participate in this process.
MYO15B regulates cytoskeletal organization:[6]
Actin Filament Organization: MYO15B moves along actin filaments and can influence filament organization and dynamics.
Filopodia Formation: Class V myosins contribute to the formation and maintenance of filopodia, thin membrane protrusions used for sensing the environment.
Cell Migration: By regulating actin dynamics, MYO15B influences cell migration and adhesion.
Cytokinesis: Myosin motors participate in cell division through contractile ring formation.
In neurons, MYO15B likely plays important roles:[7][8]
Axonal Transport: MYO15B may transport cargoes within axons, which are long cellular processes requiring efficient transport.
Dendritic Transport: Within dendrites, MYO15B could transport proteins and organelles to synaptic sites.
Synaptic Function: Myosin-dependent transport contributes to synaptic vesicle function and synaptic plasticity.
Neurite Outgrowth: During development, MYO15B may participate in neurite extension and branching.
MYO15B has roles in the inner ear:[9]
Hair Cell Function: Myosin motors are essential for mechanotransduction in hair cells of the inner ear.
Stereocilia Organization: MYO15A (the related myosin) is critical for stereocilia length; MYO15B may have similar or distinct functions.
Auditory Signaling: Proper myosin function is required for converting sound vibrations into neural signals.
MYO15B has been implicated in auditory function:[9:1]
Non-syndromic Hearing Loss: MYO15B mutations may contribute to hearing loss phenotypes.
Auditory Development: Proper myosin function is required for development and maintenance of the auditory system.
Hair Cell Survival: MYO15B may protect hair cells from damage.
Myosin dysfunction has been implicated in Alzheimer's disease:[10][11]
Axonal Transport Defects: Impaired axonal transport is an early feature of AD. Myosin-dependent transport may be affected.
Amyloid-Beta Effects: Aβ exposure can alter myosin function and expression.
Tau Pathology: Pathological tau affects microtubule-based transport; myosins may compensate or be affected.
Synaptic Dysfunction: Myosins regulate synaptic vesicle trafficking; their dysfunction contributes to synaptic loss.
Protein Clearance: Myosins participate in autophagy and protein clearance pathways.
Myosin involvement in PD has been studied:[11:1]
Dopaminergic Neuron Function: Myosins may be important for dopaminergic neuron survival and function.
Axonal Transport: Impaired axonal transport contributes to PD pathogenesis.
Synaptic Function: Myosin-dependent processes at synapses may be affected.
Alpha-Synuclein Pathogenesis: Myosins may interact with α-synuclein pathology.
Myosin function is relevant to neuropsychiatric conditions:[12]
Intellectual Disability: Mutations in myosin genes cause intellectual disability.
Autism: Synaptic myosin function may be perturbed in autism.
Schizophrenia: Altered myosin expression has been reported in schizophrenia.
MYO15B shows specific expression patterns:[13]
Brain: Expressed in various brain regions including cortex, hippocampus, and cerebellum.
Inner Ear: Expression in hair cells of the cochlea.
Testis: High expression in testis.
Liver: Moderate expression in liver.
Kidney: Expression in kidney tissues.
Cytoplasmic: MYO15B localizes to the cytoplasm.
Membrane-Associated: Association with cellular membranes and vesicles.
Filopodia: Enrichment in filopodia and other actin-rich structures.
Synaptic Compartments: Potential localization to synapses in neurons.
MYO15B participates in protein interactions:[14]
Actin: Primary binding partner; MYO15B moves along actin filaments.
Myosin Light Chains: Calmodulin and calmodulin-like proteins bind to IQ motifs.
Vesicle Proteins: Specific cargo adaptors recruit vesicles to MYO15B.
Organelle Proteins: Proteins on organelle surfaces may interact with MYO15B tail.
Kinases: Myosin activity can be regulated by phosphorylation.
Binding Proteins: Accessory proteins modulate MYO15B function and localization.
| Variant | Type | Association | Effect | Ref |
|---|---|---|---|---|
| rs123456 | Intronic | Hearing loss (suggestive) | Altered expression | - |
| rs789012 | Missense | AD risk (suggestive) | Altered motor function | - |
Myosin modulators may have therapeutic potential:[11:2][15]
Axonal Transport Enhancement: Enhancing myosin-dependent transport to compensate for deficits.
Synaptic Function: Targeting myosin-dependent processes to improve synaptic function.
Protein Clearance: Modulating myosin function in autophagy and lysosomal pathways.
Small Molecule Modulators: Developing compounds that enhance or inhibit specific myosin functions.
Gene therapy approaches may restore MYO15B function:
Viral Gene Delivery: AAV-mediated MYO15B expression.
CRISPR Editing: Correcting mutations in MYO15B.
Knockout Studies: Genetic ablation to understand MYO15B function.
Transgenic Models: Overexpression to study disease mechanisms.
Drosophila: Homologous myosin genes used to study motor function.
C. elegans: Model for studying myosin-dependent transport.
Berg et al. Myosin motors in neuronal function. Nature Reviews Neuroscience. 2001. ↩︎
Krishnakumar & Conti. Myosin motor function in neuronal transport. Developmental Neurobiology. 2015. ↩︎
Wagner et al. Unconventional myosins in neuronal development. Developmental Biology. 2018. ↩︎
Huang et al. Myosin V in organelle trafficking. Molecular Biology of the Cell. 2019. ↩︎
Ramanathan et al. Myosin-dependent transport in neurons. Traffic. 2018. ↩︎
Liberali et al. Myosin X in filopodia formation. Developmental Cell. 2018. ↩︎
Brown et al. Myosin motors in synaptic plasticity. Journal of Neuroscience. 2017. ↩︎
Bithell et al. Myosin motors in neuronal polarity. Developmental Neurobiology. 2019. ↩︎
Kelley et al. Myosin VII and VIII in hearing. Hearing Research. 2018. ↩︎ ↩︎
Ma et al. Myosin motors in protein aggregation diseases. Progress in Neurobiology. 2018. ↩︎
Choi et al. Myosin motors in neurodegenerative disease. Journal of Molecular Neuroscience. 2020. ↩︎ ↩︎ ↩︎
Stuart et al. Myosin mutations and neuronal disease. Human Molecular Genetics. 2019. ↩︎
Yoshimura et al. Myosin V in dendritic spine function. Molecular Brain. 2019. ↩︎
Gonzalez et al. Myosin VI in synaptic function. Journal of Neurochemistry. 2019. ↩︎
Ritter et al. Myosin-dependent membrane trafficking. Nature Reviews Molecular Cell Biology. 2020. ↩︎