TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

Abstract

Myosins of class VI (MYO6) are unique actin‐based motor proteins that move cargo towards the minus ends of actin filaments. As the sole myosin with this directionality, it is critically important in a number of biological processes. Indeed, loss or overexpression of MYO6 in humans is linked to a variety of pathologies including deafness, cardiomyopathy, neurodegenerative diseases as well as cancer. This myosin interacts with a wide variety of direct binding partners such as for example the selective autophagy receptors optineurin, TAX1BP1 and NDP52 and also Dab2, GIPC, TOM1 and LMTK2, which mediate distinct functions of different MYO6 isoforms along the endocytic pathway. Functional proteomics has recently been used to identify the wider MYO6 interactome including several large functionally distinct multi‐protein complexes, which highlight the importance of this myosin in regulating the actin and septin cytoskeleton. Interestingly, adaptor‐binding not only triggers cargo attachment, but also controls the inactive folded conformation and dimerisation of MYO6. Thus, the C‐terminal tail domain mediates cargo recognition and binding, but is also crucial for modulating motor activity and regulating cytoskeletal track dynamics.

Loss of myosin VI expression affects acrosome/acroplaxome complex morphology during mouse spermiogenesis†

“…This confirms our previous results (using immunogold technique) showing that MYO6 localized to both Golgi sub-domains in wild-type mice males [ 12 ]. Targeting of MYO6 to different cellular compartments in mammalian cells involves a range of binding partners [ 15 ] and so we next analyzed which adaptor protein may function with MYO6 during acrosome biogenesis. We tested several MYO6 interacting proteins including TOM1/L2, GIPC1, optineurin, DOCK7, LRCH3, and LARG for their localization, and only observed the presence of TOM1/L2 in close vicinity to the Golgi complex.…”

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

“…This feature allows MYO6 to move molecules or vesicles from the plasma membrane toward the cell interior, thereby playing essential roles in regulating endocytosis [23,26,29]. This cytoskeletal motor also controls additional intracellular trafficking events, such as exocytosis and autophagy [26,29,133]. The complexity of MYO6 functions is further illustrated by its localization in the nucleus, where it participates in the regulation of gene expression [134,135].…”

Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators

“…Recently, septins have been screened as binding partners of the complex LRCH3/ DOCK7/DOCK8/MYO6 on actin filaments [172][173][174]. DOCKs, corresponding to the Dedicator of CytoKinesis family, are GEF proteins of RhoA/Rac/Cdc42 that regulate F-actin organization (for review [175]) and MT dynamics [176].…”