Abstract
Both smooth muscle (SM) and non-muscle (NM) myosin II are expressed in hollow organs such as the bladder and uterus, but their respective roles in contraction and corresponding physiological functions remain to be determined. In this report, we assessed their roles by analyzing mice deficient of Myl9, a gene encoding the SM myosin regulatory light chain (SM RLC). We find that global Myl9-deficient bladders contracted with an apparent sustained phase, despite no initial phase. This sustained contraction was mediated by NM myosin RLC (NM RLC) phosphorylation by myosin light chain kinase (MLCK). NM myosin II was expressed abundantly in the uterus and young mice bladders, of which the force was accordingly sensitive to NM myosin inhibition. Our findings reveal distinct roles of SM RLC and NM RLC in SM contraction.
Highlights
Smooth muscle (SM) cells line the walls of hollow organs, including the gastrointestinal tract, vasculature, uterus and bladder, and they maintain homeostasis and responses to imposed signals (Somlyo and Somlyo, 1994)
To determine the roles of SM and NM myosin II in hollow organs, we established a conditional knockout line on a C57BL/6 background; the Myl9 gene was inserted with two loxP sites flanking exon 2 (Supplementary Figure S1A), and the resultant mice were crossed with different Cre lines
We found that SM-specific deletion of SM myosin regulatory light chain (SM regulatory light chain (RLC)) dramatically decreased SM contraction and profoundly impaired hollow organ function
Summary
Smooth muscle (SM) cells line the walls of hollow organs, including the gastrointestinal tract, vasculature, uterus and bladder, and they maintain homeostasis and responses to imposed signals (Somlyo and Somlyo, 1994). SM contraction is initiated by crossbridge movement of SM myosin II-based thick and F-actin-based thin filaments. During this process, myosin activity is significantly stimulated by regulatory light chain (RLC) phosphorylation when in contact with actin (Rosenfeld et al, 1998). SM RLC phosphorylation by calcium/calmodulindependent myosin light chain kinase (MLCK) is fundamentally required for SM contraction and hollow organ physiological activities (Kamm and Stull, 1985; Somlyo and Somlyo, 2003; He et al, 2008, 2011, 2013; Qiao et al, 2014). We hypothesize that NM myosin II might be involved in force production
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