A novel p21-activated kinase binds the actin and microtubule networks and induces microtubule stabilization.
Coordination of the different cytoskeleton networks in the cell is of central importance for morphogenesis, organelle transport, and motility. The Rho family proteins are well characterized for their effects on the actin cytoskeleton, but increasing evidence indicates that they may also control microtubule (MT) dynamics. Here, we demonstrate that a novel Cdc42/Rac effector, X-p21-activated kinase (PAK)5, colocalizes and binds to both the actin and MT networks and that its subcellular localization is regulated during cell cycle progression. In transfected cells, X-PAK5 promotes the formation of stabilized MTs that are associated in bundles and interferes with MTs dynamics, slowing both the elongation and shrinkage rates and inducing long paused periods. X-PAK5 subcellular localization is regulated tightly, since coexpression with active Rac or Cdc42 induces its shuttling to actin-rich structures. Thus, X-PAK5 is a novel MT-associated protein that may communicate between the actin and MT networks during cellular responses to environmental conditions.
Cau
J
J
Centre de Recherche de Biochimie Macromoleculaire, Centre National de la Recherche Scientifique UPR 1086, 34293 Montpellier cedex 5, France.
Faure
S
S
Comps
M
M
Delsert
C
C
Morin
N
N
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007201:Indicator Dilution Techniques; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D011108:Polymers / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D011108:Polymers; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; C486709:X-PAK5 protein, Xenopus; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein