p120 catenin (p120ctn), an armadillo protein and component of the cadherin adhesion complex, has been found recently to induce a dendritic morphology by regulating Rho family GTPases. We have identified specific serines within the Arm repeat domain that, when mutated to alanine, promote p120ctn association with interphase microtubules, leading to microtubule reorganization and stabilization. The mutant p120ctn also localized to the mitotic spindle and centrosomes. In contrast to wild-type p120ctn, the microtubule-associated p120ctn mutant did not activate Rac1 and did not induce a dendritic morphology. In addition, we show that a basic motif within the p120ctn Arm repeat domain known to be required for the inhibition of RhoA is also required for binding to microtubules. We therefore propose that binding of p120ctn to microtubules is inversely related to its ability to regulate Rho GTPases. p120 catenin (p120ctn), an armadillo protein and component of the cadherin adhesion complex, has been found recently to induce a dendritic morphology by regulating Rho family GTPases. We have identified specific serines within the Arm repeat domain that, when mutated to alanine, promote p120ctn association with interphase microtubules, leading to microtubule reorganization and stabilization. The mutant p120ctn also localized to the mitotic spindle and centrosomes. In contrast to wild-type p120ctn, the microtubule-associated p120ctn mutant did not activate Rac1 and did not induce a dendritic morphology. In addition, we show that a basic motif within the p120ctn Arm repeat domain known to be required for the inhibition of RhoA is also required for binding to microtubules. We therefore propose that binding of p120ctn to microtubules is inversely related to its ability to regulate Rho GTPases. p120 catenin (p120ctn) 1The abbreviations used are: p120ctn, p120 catenin; TRITC, tetramethylrhodamine isothiocyanate; PBS, phosphate-buffered saline; GFP, green fluorescent protein; VSV, vesicular stomatitis virus; GTPγS, guanosine 5′-3-O-(thio)triphosphate. is a member of the armadillo family of proteins and localizes to intercellular junctions and the nucleus (1Anastasiadis P.Z. Reynolds A.B. J. Cell Sci. 2000; 113: 1319-1334Crossref PubMed Google Scholar). In epithelial cells p120ctn localizes to adherens junctions by binding to the juxtamembrane domain of E-cadherin (2Staddon J.M. Smales C. Schulze C. Esch F.S. Rubin L.L. J. Cell Biol. 1995; 130: 369-381Crossref PubMed Scopus (139) Google Scholar, 3Shibamoto S. Hayakawa M. Takeuchi K. Hori T. Miyazawa K. Kitamura N. Johnson K.R. Wheelock M.J. Matsuyoshi N. Takeichi M. Ito F. J. Cell Biol. 1995; 128: 949-957Crossref PubMed Scopus (244) Google Scholar, 4Daniel J.M. Reynolds A.B. Mol. Cell. Biol. 1995; 15: 4819-4824Crossref PubMed Google Scholar, 5Reynolds A.B. Daniel J.M. Mo Y.Y. Wu J. Zhang Z. Exp. Cell Res. 1996; 225: 328-337Crossref PubMed Scopus (128) Google Scholar, 6Reynolds A.B. Daniel J. McCrea P.D. Wheelock M.J. Wu J. Zhang Z. Mol. Cell. Biol. 1994; 14: 8333-8342Crossref PubMed Google Scholar). In contrast to β- and γ-catenin, which act via α-catenin to link the E-cadherin complex to actin filaments, p120ctn does not appear to be involved in anchoring the E-cadherin complex to the actin cytoskeleton. Recently, p120ctn has been shown to have a supporting (7Myster S.H. Cavallo R. Anderson C.T. Fox D.T. Peifer M. J. Cell Biol. 2003; 160: 433-449Crossref PubMed Scopus (112) Google Scholar) but not essential role in Drosophila E-cadherin-mediated adhesion (7Myster S.H. Cavallo R. Anderson C.T. Fox D.T. Peifer M. J. Cell Biol. 2003; 160: 433-449Crossref PubMed Scopus (112) Google Scholar, 8Pacquelet A. Lin L. Rorth P. J. Cell Biol. 2003; 160: 313-319Crossref PubMed Scopus (78) Google Scholar). It is nevertheless believed that p120ctn is important for proper E-cadherin-mediated adhesion in mammalian cells, although whether it acts positively (9Yap A.S. Niessen C.M. Gumbiner B.M. J. Cell Biol. 1998; 141: 779-789Crossref PubMed Scopus (464) Google Scholar, 10Thoreson M.A. Anastasiadis P.Z. Daniel J.M. Ireton R.C. Wheelock M.J. Johnson K.R. Hummingbird D.K. Reynolds A.B. J. Cell Biol. 2000; 148: 189-202Crossref PubMed Scopus (389) Google Scholar) or negatively (11Ozawa M. Kemler R. J. Cell Biol. 1998; 142: 1605-1613Crossref PubMed Scopus (150) Google Scholar, 12Aono S. Nakagawa S. Reynolds A.B. Takeichi M. J. Cell Biol. 1999; 145: 551-562Crossref PubMed Scopus (200) Google Scholar) to regulate E-cadherin clustering is not clear. p120ctn-binding may also have a stabilizing effect on the E-cadherin protein (13Ireton R.C. Davis M.A. van Hengel J. Mariner D.J. Barnes K. Thoreson M.A. Anastasiadis P.Z. Matrisian L. Bundy L.M. Sealy L. Gilbert B. van Roy F. Reynolds A.B. J. Cell Biol. 2002; 159: 465-476Crossref PubMed Scopus (439) Google Scholar), possibly by preventing its ubiquitination and proteasomal degradation (14Fujita Y. Krause G. Scheffner M. Zechner D. Leddy H.E. Behrens J. Sommer T. Birchmeier W. Nat. Cell Biol. 2002; 4: 222-231Crossref PubMed Scopus (689) Google Scholar). p120ctn was originally identified as an Src tyrosine kinase substrate (15Reynolds A.B. Kanner S.B. Wang H.C. Parsons J.T. Mol. Cell. Biol. 1989; 9: 3951-3958Crossref PubMed Scopus (135) Google Scholar), and the Src phosphorylation sites have been mapped recently (16Mariner D.J. Anastasiadis P. Keilhack H. Bohmer F.D. Wang J. Reynolds A.B. J. Biol. Chem. 2001; 276: 28006-28013Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). Tyrosine phosphorylation has been suggested to increase the affinity of p120ctn for cadherins (17Calautti E. Cabodi S. Stein P.L. Hatzfeld M. Kedersha N. Paolo Dotto G. J. Cell Biol. 1998; 141: 1449-1465Crossref PubMed Scopus (223) Google Scholar, 18Kinch M.S. Clark G.J. Der C.J. Burridge K. J. Cell Biol. 1995; 130: 461-471Crossref PubMed Scopus (281) Google Scholar), but the exact influence of tyrosine phosphorylation on p120ctn is unknown. p120ctn is also phosphorylated on a number of serine/threonine residues (12Aono S. Nakagawa S. Reynolds A.B. Takeichi M. J. Cell Biol. 1999; 145: 551-562Crossref PubMed Scopus (200) Google Scholar, 19Downing J.R. Reynolds A.B. Oncogene. 1991; 6: 607-613PubMed Google Scholar, 20Ratcliffe M.J. Rubin L.L. Staddon J.M. J. Biol. Chem. 1997; 272: 31894-31901Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 21Ratcliffe M.J. Smales C. Staddon J.M. Biochem. J. 1999; 338: 471-478Crossref PubMed Scopus (61) Google Scholar, 22Ohkubo T. Ozawa M. J. Biol. Chem. 1999; 274: 21409-21415Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar). The serine/threonine phosphorylation state of p120ctn correlates with its intracellular localization. Membrane-associated, E-cadherin-bound p120ctn is highly phosphorylated, whereas cytoplasmic p120ctn shows much reduced phosphorylation levels (10Thoreson M.A. Anastasiadis P.Z. Daniel J.M. Ireton R.C. Wheelock M.J. Johnson K.R. Hummingbird D.K. Reynolds A.B. J. Cell Biol. 2000; 148: 189-202Crossref PubMed Scopus (389) Google Scholar), suggesting that p120ctn is phosphorylated by membrane-associated kinases. Serine phosphorylation events within the N terminus of p120ctn have been suggested to regulate E-cadherin clustering (12Aono S. Nakagawa S. Reynolds A.B. Takeichi M. J. Cell Biol. 1999; 145: 551-562Crossref PubMed Scopus (200) Google Scholar). In E-cadherin-deficient cancer cell lines, p120ctn is frequently observed in the nucleus (23van Hengel J. Vanhoenacker P. Staes K. van Roy F. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 7980-7985Crossref PubMed Scopus (141) Google Scholar) where it may interact with the transcription factor Kaiso (24Daniel J.M. Reynolds A.B. Mol. Cell. Biol. 1999; 19: 3614-3623Crossref PubMed Scopus (342) Google Scholar). Matrilysin/MMP7, a matrix metalloproteinase, has been implicated as a target gene for Kaiso (25Daniel J.M. Spring C.M. Crawford H.C. Reynolds A.B. Baig A. Nucleic Acids Res. 2002; 30: 2911-2919Crossref PubMed Scopus (207) Google Scholar), but the significance of the p120ctn/Kaiso interaction remains to be established. In addition to its role in cadherin-mediated adhesion, p120ctn has recently been found to be a regulator of Rho family GTPases (26Anastasiadis P.Z. Reynolds A.B. Curr. Opin. Cell Biol. 2001; 13: 604-610Crossref PubMed Scopus (229) Google Scholar), key players in coordinating a variety of cellular processes, including cell polarity, cell migration, and cell adhesion (27Ridley A.J. Trends Cell Biol. 2001; 11: 471-477Abstract Full Text Full Text PDF PubMed Scopus (644) Google Scholar). Overexpression of p120ctn in fibroblasts induces a so-called “dendritic morphology,” characterized by the extension of branching dendrite-like protrusions (5Reynolds A.B. Daniel J.M. Mo Y.Y. Wu J. Zhang Z. Exp. Cell Res. 1996; 225: 328-337Crossref PubMed Scopus (128) Google Scholar). The induction of a dendritic morphology by p120ctn involves inhibition of RhoA (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar) and activation of Rac and Cdc42 (29Grosheva I. Shtutman M. Elbaum M. Bershadsky A.D. J. Cell Sci. 2001; 114: 695-707Crossref PubMed Google Scholar, 30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). p120ctn might inhibit RhoA via a direct interaction (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar), whereas the activation of Rac and Cdc42 has been suggested to occur via binding of the guanine nucleotide exchange factor Vav2 (30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). The Arm repeat domain of p120ctn is required for the interaction with E-cadherin (4Daniel J.M. Reynolds A.B. Mol. Cell. Biol. 1995; 15: 4819-4824Crossref PubMed Google Scholar). There is evidence that the Arm repeat domain is also involved in the inhibition of RhoA (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar), and cadherin-binding and Rho GTPase regulation have been proposed to be mutually exclusive events (30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). We report here that p120ctn can associate with microtubules and that this requires a basic motif in the Arm repeat domain. Our results with different p120ctn mutants suggest that binding of p120ctn to microtubules is inversely related to its ability to regulate Rho GTPases. Cell Culture—MDA-MB-231 and COS-7 cells were grown in Dulbecco's modified Eagle's medium containing 10% bovine fetal calf serum, penicillin (100 IU/ml), and streptomycin (100 μg/ml). For NIH 3T3 fibroblasts, fetal calf serum was substituted with donor calf serum. Cells were grown in a humidified atmosphere containing 10% CO2 (COS-7, NIH 3T3) or 5% CO2 (MDA-MB-231) and passaged every 3–4 days or before reaching confluency. Antibodies—The following antibodies were used: mouse anti-VSV glycoprotein clone P5D4, mouse monoclonal anti-β-tubulin TUB 2.1, mouse monoclonal anti-acetylated tubulin clone 6-11B-1, rabbit polyclonal anti-γ-tubulin (all Sigma), mouse monoclonal anti-p120ctn (Transduction Laboratories), rabbit anti-Rac1 (Upstate Biotechnology, Inc.), fluorescein isothiocyanate-conjugated donkey anti-mouse IgG, Cy5-conjugated goat anti-mouse IgG (both Jackson ImmunoResearch), TRITC-conjugated goat anti-rabbit IgG (Southern Biotechnology Associates), and sheep horseradish peroxidase-conjugated anti-mouse IgG (Amersham Biosciences). Transfection—For COS-7 cells were grown in to and the before was cells in a cells were in and of this was For cells were in the before and were to the was used to NIH 3T3 Cells were cells in the before and the was following the Cells were to for to before or a the terminus of p120ctn, (30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar) was with and to a and the of p120ctn was and the was with an by and with and to a containing the of by the The and of p120ctn were in which a by an been by G. of p120ctn and and of were the The of was by Rac 3T3 cells were cells in cells were with or for cells were with phosphate-buffered in of Rac and for was to Rac levels in the cell the of the was with of (Upstate Biotechnology, for For in of as and and or was to of for nucleotide exchange was by to a of and was by of the with of for were in and in of the were by protein and containing of proteins were 10% and and were with antibodies the were and with antibodies to the to levels of the were and were in for and with for The cells were for with antibodies anti-β-tubulin and anti-γ-tubulin in bovine serum by with antibodies isothiocyanate-conjugated anti-mouse TRITC-conjugated anti-rabbit and Cy5-conjugated anti-mouse or with for and in was with an an a Serine to in the Arm of p120ctn with have recently identified phosphorylation sites in p120ctn A.J. C. K. A. R. Chem. 2003; PubMed Scopus Google Scholar). of a number of residues in the N and terminus and in the Arm repeat domain of p120ctn were mutated to We did not phosphorylation sites within the Arm repeat domain of of the in COS-7 cells that p120ctn mutants to within the Arm repeat and and localized interphase microtubules in of cells, whereas wild-type p120ctn did not to microtubules in cells and the and were in protein or the of COS-7 cells to and containing the or localized microtubules not of but not wild-type p120ctn, microtubules was also observed in the cell lines, 3T3 cells not and NIH 3T3 cells In cells, was with microtubules in of The association of p120ctn with microtubules did not appear to on the levels of the Cells of by of or cytoplasmic and of In COS-7 cells a of the for p120ctn microtubules was not but was in The association of with microtubules is to be as it did not with or was it in a cell not does not branching in NIH 3T3 NIH 3T3 cells were cells grown for and with of wild-type or Cells were and with anti-VSV of cells wild-type or to of of were cells were as branching or cellular the of the the of and p120ctn to and the of with was not to interphase microtubules. In COS-7 cells, localized to the mitotic spindle and to of the p120ctn to be with the mitotic but a of mutant p120ctn a the of the In contrast to the to the mitotic be the interphase suggesting that the association of p120ctn with with this a of p120ctn was or the in the cancer cell cells The of p120ctn to the in cells a role for the interaction of p120ctn with cell be identified in cells by It was therefore not to whether the association also in of p120ctn to was not observed in COS-7 or NIH 3T3 cells, possibly the of p120ctn in cells is to of a of p120ctn with to association with microtubules and and were in in the nucleus is in contrast with interphase microtubules in fibroblasts, which the and the has been to microtubule G. J. Cell Sci. PubMed Google Scholar). highly to microtubules, the of the tubulin a of J. Cell Sci. 1989; PubMed Google Scholar, J. Cell Biol. PubMed Scopus Google Scholar), as of a anti-acetylated was used to that p120ctn binding to microtubules a stabilizing effect on microtubules in cells a of tubulin was in cells or in cells with whereas the microtubule in the cells for tubulin of wild-type p120ctn did not increase the of in the of the within the cellular for tubulin suggesting that wild-type p120ctn may microtubules in a or of wild-type p120ctn is known to induce extension of protrusions (5Reynolds A.B. Daniel J.M. Mo Y.Y. Wu J. Zhang Z. Exp. Cell Res. 1996; 225: 328-337Crossref PubMed Scopus (128) Google Scholar). In did not branching in COS-7 cells cells to be The dendritic morphology is in NIH 3T3 fibroblasts (5Reynolds A.B. Daniel J.M. Mo Y.Y. Wu J. Zhang Z. Exp. Cell Res. 1996; 225: 328-337Crossref PubMed Scopus (128) Google Scholar), and this cell was therefore to the ability of wild-type and to induce dendritic In p120ctn was found to be in a dendritic morphology although and the intracellular not wild-type and were used to Overexpression of wild-type a dendritic morphology in of cells The cell was highly the and cells a number of of which for the cell The of the of dendritic In branching in 10% of cells that were and the cells Overexpression of p120ctn in fibroblasts Rac and Cdc42 (29Grosheva I. Shtutman M. Elbaum M. Bershadsky A.D. J. Cell Sci. 2001; 114: 695-707Crossref PubMed Google Scholar, 30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). Rac1 and Cdc42 required for the of Rac1 or Cdc42 with p120ctn branching (29Grosheva I. Shtutman M. Elbaum M. Bershadsky A.D. J. Cell Sci. 2001; 114: 695-707Crossref PubMed Google Scholar, 30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). whether the for the of to induce branching is the of its ability to activate Rac were van S. T. van F. J. Cell Biol. 1998; PubMed Scopus Google Scholar). NIH 3T3 cells were with wild-type or with as a In a of the was to be and The that wild-type p120ctn the levels of Rac1 in the cells and did not Rac1 levels the levels when was of the of the of Rac1 activation in to wild-type p120ctn is in the which Rac1 levels and the in Rac1 wild-type p120ctn and cells was highly results suggest that microtubule-associated p120ctn to induce branching it is to activate of a in the Arm of and of the of with microtubules with the of this mutant to induce a dendritic morphology. the microtubule binding and the dendritic we to a in p120ctn required for of p120ctn on a within Arm repeat (1Anastasiadis P.Z. Reynolds A.B. J. Cell Sci. 2000; 113: 1319-1334Crossref PubMed Google Scholar), has been shown to be required for p120ctn to induce a dendritic morphology in NIH 3T3 cells (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar). In with this wild-type the basic motif and did not induce a dendritic morphology in COS-7 cells this basic motif is also involved in microtubule were in the protein of the basic motif of to microtubules in COS-7 cells of with also microtubule whereas p120ctn with microtubules to the as that not required for microtubule binding not of the basic motif involved in the interaction of p120ctn with microtubules and the induction of the Rho dendritic morphology. p120ctn is known to associate with adherens regulate the of Rho and to the but its association with microtubules has not been We report here that p120ctn to microtubules is by serines to in the Arm repeat domain and is also on a of p120ctn to microtubules and its ability to activate Rac and induce a dendritic morphology mutually The serines and mutated to in highly in p120ctn family In Arm of p120ctn, the the is or (1Anastasiadis P.Z. Reynolds A.B. J. Cell Sci. 2000; 113: 1319-1334Crossref PubMed Google Scholar), that residues with Arm repeat The association of with microtubules may a in the Arm repeat domain that a as the motif and is it is that the serines phosphorylation sites and that phosphorylation microtubule of sites phosphorylation and microtubule we have evidence that serines phosphorylated, A.J. C. K. A. R. Chem. 2003; PubMed Scopus Google Scholar) or of The that localizes to the mitotic spindle and and that p120ctn can to the that it might regulate microtubule the Drosophila and armadillo have been shown to be required for anchoring the mitotic spindle to actin B.M. E. P. A. Peifer M. Nat. Cell Biol. 2001; PubMed Scopus (141) Google Scholar, Nat. Cell Biol. 2001; PubMed Scopus Google Scholar). the cell and be involved in anchoring spindle microtubules to the p120ctn is the known component of the E-cadherin complex to a in its phosphorylation state A. H. Kemler R. J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), with it a role in spindle a microtubules, to that observed for proteins or that interact with microtubules via proteins as or It is therefore that p120ctn is microtubules. In with p120ctn has been recently to to microtubules in cell lines, and this has been suggested to association with A. Reynolds A.B. J. Cell Sci. 2003; PubMed Scopus Google Scholar). Arm repeat proteins have been shown to to with the protein S. M. Nat. Cell Biol. 2001; PubMed Scopus Google Scholar), whereas microtubules by binding to proteins T. Y. R. R. S. K. T. Nat. Cell Biol. 2002; 4: PubMed Scopus Google Scholar). The of to induce a dendritic morphology with its of effect on Rac1 suggesting that microtubule association and Rac1 activation inversely related of p120ctn has been proposed to regulate Rho GTPases in different it RhoA via a direct interaction (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar), and it Rac and Cdc42 via the exchange factor Vav2 (30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). the activation of and the inhibition of RhoA required for p120ctn to induce the dendritic morphology (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar, I. Shtutman M. Elbaum M. Bershadsky A.D. J. Cell Sci. 2001; 114: 695-707Crossref PubMed Google Scholar, 30Noren N.K. Liu B.P. Burridge K. Kreft B. J. Cell Biol. 2000; 150: 567-580Crossref PubMed Scopus (470) Google Scholar). of Rac1 or Cdc42 is not to induce the dendritic possibly to and to extension C. A. I. J. Cell Sci. 1999; PubMed Google Scholar). In inhibition of RhoA or its target is to induce and branching H. T. H. Y. K. K. M. T. S. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, A. N. B. Z. J. G. J. 1999; PubMed Scopus Google Scholar). that the levels of Rac and RhoA inversely that Rac to RhoA J. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, van S. van J. Cell Biol. 1999; PubMed Scopus Google Scholar), and that inhibition of RhoA can induce an increase in Rac T. T. M. C. K. T. Y. T. H. S. J. Cell Biol. 2002; PubMed Scopus Google Scholar), p120ctn the of Rho and Rac by the of the basic motif and which we found to be required for p120ctn to associate with microtubules, is also required for the effect of p120ctn on RhoA (28Anastasiadis P.Z. Moon S.Y. Thoreson M.A. Mariner D.J. Crawford H.C. Zheng Y. Reynolds A.B. Nat. Cell Biol. 2000; 2: 637-644Crossref PubMed Scopus (380) Google Scholar). p120ctn the motif to to microtubules and to inhibit microtubule association to RhoA and of the effect on and to a in Rac1 microtubule binding Vav2 interaction and Rac activation and the in RhoA number of microtubule-associated as M. J. Cell Biol. 1989; PubMed Scopus Google Scholar) and the protein A. 1998; 14: PubMed Scopus Google Scholar), interact with microtubules via containing of which the motif of basic motif is highly the p120ctn family (1Anastasiadis P.Z. Reynolds A.B. J. Cell Sci. 2000; 113: 1319-1334Crossref PubMed Google Scholar) and has been proposed to be a M. M. J. Cavallo R. Peifer M. L. J. Cell Biol. 1999; PubMed Scopus Google Scholar). We observed of mutants in cells, although the of mutants was much reduced with wild-type or M. and A. J. The association of p120ctn with the microtubule has been suggested recently A. Reynolds A.B. J. Cell Sci. 2003; PubMed Scopus Google Scholar) to of In that p120ctn mutants that to associate with microtubules show localization. The link microtubule binding and of p120ctn remains to be The association of p120ctn with microtubules to and to as by the increase in microtubules within show a of with microtubules in the cell It is therefore that p120ctn with and microtubules in extension of the dendritic requires Rac and Cdc42 activation and RhoA inhibition as as microtubule E. T. J. Cell Biol. 1995; 128: PubMed Scopus Google Scholar, A. J. Cell Biol. 1999; PubMed Scopus Google Scholar). In addition, microtubules with an increase in U. Cell 1989; PubMed Scopus Google Scholar, A. A. Res. 1989; PubMed Scopus Google Scholar, Res. 1999; PubMed Scopus Google Scholar). The of p120ctn to microtubules, regulate Rho and induce a dendritic it a for an important role in In of this p120ctn localizes to and to dendritic in and its is N. M. C. N.K. A. Mol. Cell. 2003; PubMed Scopus Google Scholar) and to containing tubulin in M. and A. J. a related member of the p120ctn has been shown recently to dendritic in and to induce dendrite-like in 3T3 fibroblasts, that required the of microtubules N.K. M. M. J. Res. 2002; PubMed Scopus Google Scholar, K. A. S.B. R. C. Exp. Cell Res. 2002; PubMed Scopus Google Scholar). of p120ctn induces dendritic in M. and A. J. The dendritic morphology observed in fibroblasts therefore a for p120ctn in where it promote by stabilizing microtubules and regulating Rho GTPases.
No takes yet. Share an insight, caveat, or question.
Franz et al. (2004) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: