Myosin VI Dynamics in Cellular Processes

Myosin VI is a unique actin-based motor protein distinguished by its capacity to move towards the minus end of actin filaments. This reverse directionality underpins its roles in vesicle trafficking, organisation of endosomal compartments, genome stability and regulation of gene expression. The motor’s activity is governed by intramolecular autoinhibitory interactions between its head and tail domains, which block cargo binding and suppress ATPase activity. Binding of specialised adaptor proteins relieves this inhibition, promotes dimerisation and enables processive movement along actin tracks. Through these mechanisms, myosin VI orchestrates membrane dynamics at the cell cortex, directs intracellular signalling endosomes and anchors transcriptional machinery within the nucleus. Dysregulation of myosin VI contributes to cardiac dysfunction, deafness, neurodegeneration and cancer. Advances in structural biology and live-cell imaging have shed light on the conformational switches, adaptor interactions and post-translational modifications that integrate to fine-tune myosin VI function across spatial and temporal scales, emphasising its centrality in cellular physiology and human disease.

Research from Nature Portfolio

Recent studies have revealed the high-resolution cryo-EM structure of autoinhibited myosin VI, capturing a compact monomeric fold in which head–tail contacts occlude cargo-binding sites and repress ATPase activity. These insights clarify how specific adaptor proteins disrupt inhibitory interfaces, trigger dimerisation and activate processive motility, offering a structural rationalisation for disease-associated mutations. Complementary single-molecule imaging and genomic analyses have demonstrated that nuclear myosin VI acts as a molecular scaffold for RNA Polymerase II clusters, organising transcription initiation sites at the nanoscale. Disruption of myosin VI leads to dispersion of polymerase clusters, altered chromatin organisation and reduced gene expression. Foundational work has further shown that transcriptional co-activators relieve myosin VI autoinhibition, enabling direct binding to DNA and interaction with the transcriptional apparatus to drive gene expression.

Myosin VI Dynamics in Cellular Processes publication trend

The graph below shows the total number of articles in myosin vi dynamics in cellular processes across all publications each year (not limited to Nature Index journals).

Technical terms

Actin filaments: Polarised helical polymers of actin subunits forming tracks for myosin motor movement.

ATPase activity: Enzymatic hydrolysis of ATP that powers conformational changes and movement of motor proteins.

Autoinhibition: An internal regulatory mechanism whereby head and tail domains interact to suppress motor activity until relieved by adaptor binding.

Cargo adaptor: A protein that simultaneously binds myosin VI and its cargo, relieving autoinhibition and directing specific transport pathways.

Processivity: The ability of a motor protein to take multiple successive steps along a filament without detaching.

Cryo-electron microscopy: A technique that images proteins in a near-native frozen state at near-atomic resolution, revealing structural conformations.

References

1. Autoinhibition and activation of myosin VI revealed by its cryo-EM structure. Nature Communications (2024).
2. Myosin in chromosome organisation and gene expression. Biochemical Society Transactions (2023).
3. Unconventional myosin VI in the heart: Involvement in cardiac dysfunction progressing with age. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (2023).
4. NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications (2017).
5. MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics. Cell Reports (2017).
6. Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nature Communications (2022).
7. Loss of cargo binding in the human myosin VI deafness mutant (R1166X) leads to increased actin filament binding. Biochemical Journal (2016).