Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin.
Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of beta-catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3beta. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of beta-catenin. In the absence of Cdc42, degradation of beta-catenin was increased corresponding to a decreased phosphorylation of GSK3beta at Ser 9 and an increased phosphorylation of axin, which is known to be required for binding of beta-catenin to the degradation machinery. Cdc42-mediated regulation of beta-catenin turnover was completely dependent on PKCzeta, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of beta-catenin turnover is important for terminal differentiation of HF progenitor cells in vivo.
Wu
Xunwei
X
Max Planck Institute of Biochemistry, Heisenberg Group Regulation of Cytoskeletal Organization, Department of Molecular Medicine, 82152 Martinsried, Germany.
Quondamatteo
Fabio
F
Lefever
Tine
T
Czuchra
Aleksandra
A
Meyer
Hannelore
H
Chrostek
Anna
A
Paus
Ralf
R
Langbein
Lutz
L
Brakebusch
Cord
C
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D060466:Axin Protein; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D019070:Cell Lineage; D002478:Cells, Cultured; D017353:Gene Deletion; D018390:Gene Targeting; D017930:Genes, Reporter; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D013234:Stem Cells; D051176:beta Catenin / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D060466:Axin Protein; D012097:Repressor Proteins; D051176:beta Catenin; D008156:Luciferases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D020764:cdc42 GTP-Binding Protein