MSAP enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain.
A key regulatory mechanism in cell motility is the control of myosin activity, which in non-muscle cells is determined by phosphorylation of the myosin regulatory light chain (MRLC). Here we show that MRLC-interacting protein (MIR)-interacting saposin-like protein (MSAP) enhances cell spreading in fibroblasts and migration of rat C6 glioma cells through increases in MRLC phosphorylation. Overexpression of MSAP enhanced the motility of glioma cells measured in matrigel invasion chambers and using a scratch assay. Downregulation of MSAP by RNA interference significantly decreased glioma cell migration and phosphorylation of MRLC. Inhibition of the corresponding MRLC kinase by ML-7 did not affect migration of MSAP-overexpressing cells. The present results show that MSAP controls glioma cell migration via enhancement of MRLC phosphorylation. This effect is independent of the activity of MRLC kinase. Thus, MSAP is a novel modulator of cell motility that influences migration of glioma cells and possibly other tumors.
Bornhauser
B C
BC
Department of Neuroscience, Neurobiology, Biomedical Centre, Uppsala University, Box 587, 75123 Uppsala, Sweden. beat.bornhauser@neuro.uu.se
Lindholm
D
D
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D018994:Myosin Light Chains / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D049231:Saposins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D002352:Carrier Proteins; C502334:MSAP protein, rat; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; D049231:Saposins