Beyond regulation of cell adhesion: local control of RhoA at the cleavage furrow by the p0071 catenin.
P120(ctn) is the prototype of a subfamily of armadillo proteins that also comprises p0071, delta-catenin, ARVCF and the more distantly related plakophilins 1-3. These proteins have well established roles in regulating adherens junction and desmosome formation which critically depends on their capacity to cluster cadherins. Besides this function in cell adhesion that is mediated by a membrane associated pool, these proteins also show cytoplasmic and nuclear localization. While their nuclear function is still enigmatic, major progress in understanding their cytoplasmic role has been made. In the cytoplasm, the p120 catenins appear responsible for the spatio-temporal control of small Rho-GTPases in various cellular contexts. Whereas p120(ctn) has a major function in regulating cell adhesion and motility through controlling Rho-GTPases, a recent report shows that the closely related protein p0071 associates and regulates RhoA at the cleavage furrow during cytokinesis. Overexpression and knockdown of p0071 induced a cytokinesis defect that was mediated by up- or downregulation of RhoA activity at the contractile ring. There, p0071 interacted directly with RhoA itself and with the Rho-GEF Ect2. Full activation of RhoA required Ect2 as well as p0071 indicating that these two proteins act in conjunction to regulate RhoA during cytokinesis. Here we discuss the function of p120 catenins as versatile scaffolds that confer specificity to the complex regulation of Rho-GTPases. By controlling numerous stimulating guanine exchange factors (GEFs) and inhibiting GTPase activating proteins (GAPs) via the formation of multiprotein complexes at the right time and place, they direct the spatio-temporal control of Rho-signalling.
Keil
Rene
R
Institute for Pathophysiology, Division of Pathobiochemistry, Martin Luther University-Halle, Halle, Germany.
Wolf
Annika
A
Hüttelmaier
Stefan
S
Hatzfeld
Mechthild
M
D000818:Animals; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D048749:Cytokinesis / Q000502:physiology*; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D051191:Plakophilins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; C105677:PKP4 protein, human; D010750:Phosphoproteins; D051191:Plakophilins; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human