Recruitment of a myosin heavy chain kinase to actin-rich protrusions in Dictyostelium

Nonmuscle myosin II plays fundamental roles in cell body translocation duri ng migration and is typically depleted or absent from actin-based cell prot rusions such as lamellipodia, but the mechanisms preventing myosin II assem bly in such structures have not been identified [1-3], In Dictyostelium dis coideum, myosin II filament assembly is controlled primarily through myosin heavy chain (MHC) phosphorylation, The phosphorylation of sites in the myo sin tail domain by myosin heavy chain kinase A (MHCK A) drives the disassem bly of myosin II filaments in vitro and in vivo [4] To better understand th e cellular regulation of MHCK A activity, and thus the regulation of myosin II filament assembly, we studied the in vivo localization of native and gr een fluorescent protein (GFP)-tagged MHCK A. MHCK A redistributes from the cytosol to the cell cortex in response to stimulation of Dictyostelium cell s with chemoattractant in an F-actin-dependent manner. During chemotaxis, r andom migration, and phagocytic/endocytic events, MHCK A is recruited prefe rentially to actin-rich leading-edge extensions. Given the ability of MHCK A to disassemble myosin II filaments, this localization may represent a fun damental mechanism for disassembling myosin II filaments and preventing loc alized filament assembly at sites of actin-based protrusion.