The MYO 6 interactome: selective motor‐cargo complexes for diverse cellular processes

• Published in: FEBS letters Vol. 593; no. 13; pp. 1494 - 1507
• Main Authors: de Jonge, Janeska J., Batters, Christopher, O'Loughlin, Thomas, Arden, Susan D., Buss, Folma
• Format: Journal Article
• Language: English
• Published: 01-07-2019
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.13486

Myosins of class VI ( MYO 6) 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 MYO 6 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, TAX 1 BP 1 and NDP 52 and also Dab2, GIPC , TOM 1 and LMTK 2, which mediate distinct functions of different MYO 6 isoforms along the endocytic pathway. Functional proteomics has recently been used to identify the wider MYO 6 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 MYO 6. Thus, the C‐terminal tail domain mediates cargo recognition and binding, but is also crucial for modulating motor activity and regulating cytoskeletal track dynamics.