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Regulation of leading edge microtubule and actin dynamics downstream of Rac1.

http://www.ncbi.nlm.nih.gov/pubmed/12796474

Actin in migrating cells is regulated by Rho GTPases. However, Rho proteins might also affect microtubules (MTs). Here, we used time-lapse microscopy of PtK1 cells to examine MT regulation downstream of Rac1. In these cells, "pioneer" MTs growing into leading-edge protrusions exhibited a decreased catastrophe frequency and an increased time in growth as compared with MTs further from the leading edge. Constitutively active Rac1(Q61L) promoted pioneer behavior in most MTs, whereas dominant-negative Rac1(T17N) eliminated pioneer MTs, indicating that Rac1 is a regulator of MT dynamics in vivo. Rac1(Q61L) also enhanced MT turnover through stimulation of MT retrograde flow and breakage. Inhibition of p21-activated kinases (Paks), downstream effectors of Rac1, inhibited Rac1(Q61L)-induced MT growth and retrograde flow. In addition, Rac1(Q61L) promoted lamellipodial actin polymerization and Pak-dependent retrograde flow. Together, these results indicate coordinated regulation of the two cytoskeletal systems in the leading edge of migrating cells.

Pubmed ID: 12796474 RIS Download

Mesh terms: Actin Cytoskeleton | Animals | Cell Movement | Cell Polarity | Cells, Cultured | Enzyme Inhibitors | Eukaryotic Cells | Microscopy, Video | Microtubules | Mutation | Protein-Serine-Threonine Kinases | Pseudopodia | p21-Activated Kinases | rac1 GTP-Binding Protein

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