Within eukaryotic cells, myosin motor proteins move cargo over short distances along actin tracks, regulate plasma membrane dynamics through the actin cortex and provide flexible tethering of organelles, vesicles and protein complexes to the actin cytoskeleton. Myosins of class I are widely expressed monomeric single-headed motors. The biological functions of class I myosins are at the membrane–cytoskeleton interface, where they provide mechanical force and tension that allows remodelling of membranes relative to the underlying actin network.
MYO1F, a long-tailed myosin of class I, is selectively expressed in immune cells and upregulated in microglia associated with neurodegenerative pathogenesis. Myosin motor functions are regulated by adaptor proteins that mediate cargo attachment and motor recruitment. In this paper from the Buss lab, Sue Arden has used in situ proximity labelling and proteomics to define the MYO1F interactome in human myeloid cells. A distinct SH3-domain-dependent adaptor module comprising CD2AP, ASAP1, SH3BP2 and SH3KBP1 (termed the CASS group of proteins) was identified. Interestingly, CD2AP is an Alzheimer's disease (AD) risk gene upregulated in microglia, which are implicated in phagocytic responses to amyloid-β. This paper provides the first MYO1F interactome identifying adaptor proteins for MYO1F in podosomes and during phagocytosis, offering new insights into its function in disease-associated microglia during neurodegeneration.