FUNCTIONAL CHARACTERIZATION OF MYOSIN VI IN CENTROSOME BIOLOGY AND CELL CYCLE PROGRESSION

Myosin VI is a unique actin motor involved in multiple biological functions, such as endocytic and secretion processes, cell migration, autophagy, and in the maintenance of the Golgi complex and stereocilia. These functions are dictated by the interaction of myosin VI with different cargos, which can also regulate the ability of this protein to work as an anchor or a motor that moves along actin filaments. Previous experiments performed in our laboratory led to the identification of a novel set of myosin VI interactors that belong to the centrosome compartment, suggesting that myosin VI could have an important and unexpected role in centrosomal processes. Indeed, the depletion of myosin VI leads to alterations in the centrosome structure and number, and to an impairment in the formation of the primary cilium. Our data also suggest a potential role of myosin VI in the regulation of cell cycle progression. Indeed, myosin VI depletion leads to cell cycle arrest and senescence caused by p53 activation. To characterize this phenotype, we performed a genome-wide CRISPR/Cas9 rescue screening, that led us to identify some candidates potentially involved in p53 activation following myosin VI depletion. This study unveils a new role for myosin VI in centrosome biology and in the control of the cell cycle, two processes whose dysregulation is an important step during carcinogenesis.