title: Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility.
abstract: Directional motility is a fundamental function of immune cells, which are recruited to sites of pathogen invasion or tissue damage by chemoattractant signals. To move, cells need to generate lamellipodial membrane protrusions at the front and retract the trailing end. These elementary events are initiated by Rho-family GTPases, which cycle between active GTP-bound and inactive GDP-bound states. How the activity of these "molecular switches" is spatially coordinated is only beginning to be understood. Here, we show that myosin IXb (Myo9b), a Rho GTPase-activating protein (RhoGAP) expressed in immune cells, is essential for coordinating the activity of Rho. We generated Myo9b-deficient mice and show that Myo9b(-/-) macrophages have strikingly defective spreading and polarization. Furthermore, Myo9b(-/-) macrophages fail to generate lamellipodia in response to a chemoattractant, and migration in a chemotactic gradient is severely impaired. Inhibition of Rho rescues the Myo9b(-/-) phenotype, but impairs tail retraction. We also found that Myo9b is important in vivo. Chemoattractant-induced monocyte recruitment to the peritoneal cavity is substantially reduced in Myo9b(-/-) mice. Thus, we identify the "motorized Rho inhibitor" Myo9b as a key molecular component required for spatially coordinated cell shape changes and motility.
authors.affiliation: Institut für Physiologie II, Westfälische Wilhems-Universität Münster, 48149 Münster, Germany. hanley@uni-muenster.de
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hanley
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Moritz
authors.initials: M
authors.lastname: Kronlage
authors.forename: Kay
authors.initials: K
authors.lastname: Grobe
authors.forename: Peter
authors.initials: P
authors.lastname: Schön
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schwab
authors.forename: Martin
authors.initials: M
authors.lastname: Bähler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D048430:Cell Shape / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics / Q000502:physiology; D005260:Female; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
chemical_list: C113469:myosin IXB; D009218:Myosins