Key pointsr Force production and maintenance in smooth muscle is largely controlled by myosin regulatory light chain (RLC) phosphorylation, which relies on a balance between Ca 2+ /calmodulindependent myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities.r MYPT1 is the regulatory subunit of MLCP that biochemically inhibits MLCP activity via T694 or T852 phosphorylation in vitro.r Here we separately investigated the contribution of these two phosphorylation sites in bladder smooth muscles by establishing two single point mutation mouse lines, T694A and T852A, and found that phosphorylation of MYPT1 T694, but not T852, mediates force maintenance via inhibition of MLCP activity and enhancement of RLC phosphorylation in vivo.r Our findings reveal the role of MYPT1 T694/T852 phosphorylation in vivo in regulation of smooth muscle contraction.Abstract Force production and maintenance in smooth muscle is largely controlled by different signalling modules that fine tune myosin regulatory light chain (RLC) phosphorylation, which relies on a balance between Ca 2+ /calmodulin-dependent myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities. To investigate the regulation of MLCP activity in vivo, we analysed the role of two phosphorylation sites on MYPT1 (regulatory subunit of MLCP) that biochemically inhibit MLCP activity in vitro. MYPT1 is constitutively phosphorylated at T694 by unidentified kinases in vivo, whereas the T852 site is phosphorylated by RhoA-associated protein kinase (ROCK). We established two mouse lines with alanine substitution of T694 or T852. Isolated bladder smooth muscle from T852A mice displayed no significant changes in RLC phosphorylation or force responses, but force was inhibited with a ROCK inhibitor. In contrast, smooth muscles containing the T694A mutation showed a significant reduction of force along with reduced RLC phosphorylation. The contractile responses of T694A mutant smooth muscle were also independent of ROCK activation. Thus, phosphorylation of MYPT1 T694, but not T852, is a primary mechanism contributing to inhibition of MLCP activity and enhancement of RLC phosphorylation in vivo. The constitutive phosphorylation of MYPT1 T694 may provide a mechanism for regulating force maintenance of smooth muscle.
Nanomaterials play crucial roles in the diagnosis and treatment of diseases. Photothermal and photodynamic therapy, as two minimally invasive therapeutic methods, have promising potential in the diagnosis and prevention of cancer. Recently, many photothermal materials (such as noble metal material, transition metal sulfur oxides, carbon material and upconversion nanomaterial) and photodynamic materials (such as phthalein cyanogen, porphyrins and other dye molecules) have been applied in photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, as nanomaterials have suitable biocompatibility, these materials have been applied in cancer therapy. In the present review, we summarized the effects of different material types, synthesis methods, material morphologies and surface modifications on the outcomes of cancer therapy. The application of nanomaterials in PTT and PDT was introduced and the advantages and disadvantages of PTT and PDT in the prevention of cancer were discussed. Finally, we discussed the application of nanomaterials in the combination of PTT and PDT in cancer treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.