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Spatial regulation of myosin light chain phosphorylation through differentially localized phosphatase isoforms
Author(s) -
Neppl R L,
Eto M,
Somlyo A P,
Somlyo A V
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a924-c
Subject(s) - myosin light chain phosphatase , microbiology and biotechnology , myosin light chain kinase , myosin , biology , phosphorylation , rhoa , rho associated protein kinase , cytoskeleton , filamin , moesin , alternative splicing , focal adhesion , ezrin , gene isoform , biochemistry , signal transduction , cell , gene
The opposing actions of myosin light chain kinase and myosin light chain phosphatase (MLCP) determine the level of myosin regulatory light chain (RLC) phosphorylation and thereby determine the generation of force in smooth muscle (SM) as well as non‐muscle myosin II regulated cell migration. The MLCP regulatory subunit (MYPT1) is expressed as two isoforms due to alternative splicing of a central exon. Testing the hypothesis that the two MYPT1 splice variants have different functions, we quantify the expression of the MYPT1 exon‐inclusion isoform (MYPT1‐L) to account for 70 – 90% of total MYPT1 protein in vascular and visceral SM. Endogenous MYPT1‐L co‐localized with stress fibers in cultured SMCs, while over‐expressed MYPT1‐S localizes to the lamellipodia of migrating cells. We hypothesize that MYPT1‐S dephosphorylates members of the Ezrin/Radixin/Moesin family of proteins in the lamellipodium, and opposes the actions of Rho Kinase and MLCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration. Further, we demonstrate translocation of MYPT1 from the cytosol to SMC membranes in rat cerebral vessels upon stimulation with the RhoA‐activating phospholipid sphingosine‐1‐phosphate, and suggest that the translocation results in increased RLC20 phosphorylation, in part due to its absence from the actin‐myosin contractile apparatus, and by phospho‐inhibition of MYPT1. In summary, we propose that the spatial distributions of MYPT1 isoforms are indicative of specialized roles for controlling Ser/Thr phosphorylation of focal adhesions and cytoskeletal proteins. Supported by NIH POI HL48807