Published in Cell. 2008. Oct 3. 135: 123-136
Ivan Tan1, Jeffery Yong1,2, Jing Ming Dong1, Louis Lim1,3, THomas Leung1,2
1 From the GSK-IMCB Group, Institute of Molecular & Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore
2 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore.
3 Department of Molecular Neuroscience, Institute of Neurology, University College London, 1 Wakefield Street, London WC1N 1PJ, United Kingdom.
Cell movement involves a cycle of steps within different zones, including protrusion of lamellipodia at the front, formation of adhesions there and their disruption at the rear, and finally contraction in the lamella and accompanying retraction at the rear. Retrograde flow of actin and myosin motor proteins in lamellipodia and lamella is essential for membrane protrusion and for contraction. We report that kinase MRCK and myosin 18A are linked by adaptor protein LRAP35a to form a tripartite complex, which is responsible for the assembly of lamellar actomyosin bundles whose retrograde flow is essential for cell protrusion and migration.
Figure Legend (A) Endogenous MRCKα, pRMLC and MYO18A display a polarized localization in the lamella of migrating cells along wound edges. This shared localization occurred within a polarized actomyosin network perpendicular to the direction of wound. [U2OS cells at wound edges were stained for F-actin with endogenous MRCKα and pRMLC (top), or MRCKα and MYO18A (bottom). Cells were fixed 2 h after wounding. Scale bar: 20μm.]
Figure Legend (B) Model of MRCK Complex Regulation of Actomyosin Bundles. The adaptor LRAP35a links MRCK, which it activates, to MYO18A via separate binding sites (leucine-rich repeats and PDZ-binding site, respectively). The MRCK complex is associated with actomyosin bundles in the lamella possibly through MYO18A, a potential actin-binding motor protein. MRCK phosphorylation of RMLC at Serine-19 is essential for motor activities of both MYO18A and the neighboring MYO2A. These activities are crucial for the assembly and thus for the flow of the actomyosin bundles. The association of the MRCK complex with the actomyosin bundles is stimulated by extracellular signals acting through Cdc42. LRAP35a through its phosphorylation by GSK-3β
may play a role in microtubule (MT) dynamics, known to be tightly coupled to the retrograde flow.
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