Engaging myosin VI tunes motility, morphology and identity in endocytosis

• Published in: Traffic (Copenhagen, Denmark) Vol. 19; no. 9; pp. 710 - 722
• Main Authors: Ritt, Michael, Sivaramakrishnan, Sivaraj
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.09.2018; Wiley Subscription Services, Inc
• Subjects: chemical dimerization; Dimerization; early endosomes; Endocytosis; Endosomes; Homeostasis; molecular motors; Morphology; Motility; Myosin; optogenetics; Organelles; synthetic biology; unconventional myosins; chemical dimerization; early endosomes; synthetic biology; unconventional myosins; optogenetics; endocytosis; molecular motors
• ISSN: 1398-9219; 1600-0854; 1600-0854
• DOI: 10.1111/tra.12583

While unconventional myosins interact with different stages of the endocytic pathway, they are ascribed a transport function that is secondary to the protein complexes that control organelle identity. Endosomes are subject to a dynamic, continuous flux of proteins that control their characteristic properties, including their motility within the cell. Efforts to describe the changes in identity of this compartment have largely focused on the adaptors present on the compartment and not on the motile properties of the compartment itself. In this study, we use a combination of optogenetic and chemical‐dimerization strategies to target exogenous myosin VI to early endosomes, and probe its influence on organelle motility, morphology and identity. Our analysis across timescales suggests a model wherein the artificial engagement of myosin VI motility on early endosomes restricts microtubule‐based motion, followed by morphological changes characterized by the rapid condensation and disintegration of organelles, ultimately leading to the enhanced overlap of markers that demarcate endosomal compartments. Together, our findings show that synthetic engagement of myosin VI motility is sufficient to alter organelle homeostasis in the endocytic pathway. Upon artificial engagement of myosin VI, endocytic motility slows down and becomes less directional on a scale of seconds. Over a course of minutes, myosin VI‐engaged organelles begin to alter their morphology. After hours of engagement, reorganization of markers conferring organelle identity is observed. Additionally, differences between the cellular activity of myosin VI monomers and dimers are observed. Our findings explore roles for myosin VI in tuning organelle homeostasis in the endocytic pathway.