4-Hydroxyacetophenone Modulates the Cytoskeleton through Nonmuscle Myosin-2C to Reduce Metastasis

PAR-4/LKB1 Mobilizes Nonmuscle Myosin through Anillin to Regulate C. elegans Embryonic Polarization and Cytokinesis

BACKGROUND The serine/threonine kinase LKB1 regulates cell growth and polarity in metazoans, and loss of LKB1 function is implicated in the development of some epithelial cancers. Despite its fundamental role, the mechanism by which LKB1 regulates polarity establishment and/or maintenance is unclear. In the present study, we use the nematode C. elegans to investigate the role of the LKB1 orthol...

Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C

Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 Å pre-powerstroke state (ADP⋅VO4) crystal structure of the human nonmuscle myosin-2C motor domain, one of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble-solution kinetics, and molecular dy...

Comparative Kinetic and Functional Characterization of the Motor Domains of Human Nonmuscle Myosin-2C Isoforms*

Nonmuscle myosins are widely distributed and play important roles in the maintenance of cell morphology and cytokinesis. In this study, we compare the detailed kinetic and functional characterization of naturally occurring transcript variants of the motor domain of human nonmuscle myosin heavy chain (NMHC)-2C. NMHC-2C is alternatively spliced both in loop-1 and loop-2. Isoform 2C0 contains no i...

Nonmuscle motility/cytoskeleton.

Nonmuscle myosin IIB links cytoskeleton to IRE1α signaling during ER stress.

Here we identify and characterize a cytoskeletal myosin protein required for IRE1α oligomerization, activation, and signaling. Proteomic screening identified nonmuscle myosin heavy chain IIB (NMHCIIB), a subunit of nonmuscle myosin IIB (NMIIB), as an ER stress-dependent interacting protein specific to IRE1α. Loss of NMIIB compromises XBP1s and UPR target gene expression with no effect on the PE...