Nonmuscle myosin II isoforms interact with sodium channel alpha subunits.

ABSTRACT: Sodium channels play pivotal roles in health and diseases due to their ability to control cellular excitability. The pore-forming ?-subunits (sodium channel alpha subunits) of the voltage-sensitive channels (i.e., Na_v1.1-1.9) and the nonvoltage-dependent channel (i.e., Na_x) share a common structural motif and selectivity for sodium ions. We hypothesized that the actin-based nonmuscle myosin II motor proteins, nonmuscle myosin heavy chain-IIA/myh9, and nonmuscle myosin heavy chain-IIB/myh10 might interact with sodium channel alpha subunits to play an important role in their transport, trafficking, and/or function. Immunochemical and electrophysiological assays were conducted using rodent nervous (brain and dorsal root ganglia) tissues and ND7/23 cells coexpressing Na_v subunits and recombinant myosins. Immunoprecipitation of myh9 and myh10 from rodent brain tissues led to the coimmunoprecipitation of Na_x, Na_v1.2, and Na_v1.3 subunits, but not Na_v1.1 and Na_v1.6 subunits, expressed there. Similarly, immunoprecipitation of myh9 and myh10 from rodent dorsal root ganglia tissues led to the coimmunoprecipitation of Na_v1.7 and Na_v1.8 subunits, but not Na_v1.9 subunits, expressed there. The functional implication of one of these interactions was assessed by coexpressing myh10 along with Na_v1.8 subunits in ND7/23 cells. Myh10 overexpression led to three-fold increase ( P?v1.8 channels expressed in ND7/23 cells. Myh10 coexpression also hyperpolarized voltage-dependent activation and steady-state fast inactivation of Na_v1.8 channels. In addition, coexpression of myh10 reduced ( P?v1.8 channels. These results indicate that nonmuscle myosin heavy chain-IIs interact with sodium channel alpha subunits subunits in an isoform-dependent manner and influence their functional properties.

SUBMITTER: Dash B 

PROVIDER: S-EPMC6052497 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature