期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：27
页码：12145-12150
DOI：10.1073/pnas.0911986107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：cell migration ; knockout ; Rho-family GTPases ; signal transduction
