Abstract
The small GTP-binding protein Ral is activated by RalGDS, one of the effector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in vivo function is largely unknown. To examine the effect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Ral did not affect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aelst LV and D'Souza-Schorey C. . 1997 Genes Dev. 11: 2295–2322.
Albright CF, Giddings BW, Liu J, Vito M and Weinberg RA. . 1993 EMBO J. 12: 339–347.
Bar Sagi D and Feramisco JR. . 1986 Science 233: 1061–1068.
Barrett K, Leptin M and Settleman J. . 1997 Cell 91: 905–915.
Blochlinger KL, Jan LY and Jan YN. . 1993 Development 117: 441–450.
Bos JL. . 1997 Biochem. Biophys. Acta 1333: M19–M31.
Cantor SB, Urano T and Feig LA. . 1995 Mol. Cell. Biol. 15: 4578–4584.
Chang EC, Barr M, Wang Y, Jung V, Xu HP and Wigler MH. . 1994 Cell 79: 131–141.
de Nooij JC and Hariharan IK. . 1995 Science 270: 983–985.
Eaton S, Wept R and Simons K. . 1996 J. Cell Biol. 135: 1277–1289.
Feig LA, Urano T and Contor S. . 1996 Trends Biochem. Sci. 21: 438–441.
Fortini ME, Simon MA and Rubin GM. . 1992 Nature 355: 559–561.
Frech M, Schlichting I, Wittinghofer A and Chardin P. . 1990 J. Biol. Chem. 265: 6353–6359.
Harden N, Loh HY, Chia W and Lim L. . 1995 Development 121: 903–914.
Hariharan IK, Hu K-Q, Asha H, Quintanilla A, Ezzel RM and Settleman J. . 1995 EMBO J. 14: 292–302.
Hay BA, Wolff T and Rubin GM. . 1994 Development 120: 2121–2129.
Higashijima S, Kojima T, Michiue T, Ishimaru S, Emori Y and Saigo K. . 1992 Genes Dev. 6: 50–60.
Hinoi T, Kishida S, Koyama S, Ikeda M, Matsuura Y and Kikuchi A. . 1996 J. Biol. Chem. 271: 19710–19716.
Hofer F, Fields S, Schneider C and Martin GS. . 1994 Proc. Natl. Acad. Sci. USA 91: 11089–11093.
Jiang H, Luo J-Q, Urano T, Frankel P, Lu Z, Foster DA and Feig LA. . 1995 Nature 378: 409–412.
Joneson T, White MA, Wigler MH and Bar Sagi D. . 1996 Science 271: 810–812.
Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G and Camonis HJ. . 1995 J. Biol. Chem. 270: 22473–22477.
Karim FD and Rubin GM. . 1998 Dev. 125: 1–9.
Kikuchi A, Demo SD, Ye Z-H, Chen YW and Williams LT. . 1994 Mol. Cell. Biol. 14: 7483–7491.
Kimmel BE, Heberlein U and Rubin GM. . 1990 Genes Development 4: 712–727.
Kishida S, Koyama S, Matsubara K, Kishida M, Matsuura Y and Kikuchi A. . 1997 Oncogene 15: 2899–2907.
Lee T, Feig L and Montell DJ. . 1996 Development 122: 409–418.
Leevers SL, Weinkove D, MacDougail K, Hafen E and Waterfield MD. . 1996 EMBO J. 15: 6584–6594.
Longley Jr RL and Ready DF. . 1995 Dev. Biol. 171: 415–433.
Luo L, Liao YJ, Jan LY and Jan YN. . 1994 Genes Dev. 8: 1787–1802.
Marshall CJ. . 1996 Curr. Opin. Cell Biol. 8: 197–204.
Matsuo T, Takahashi K, Kondo S, Kaibuchi K and Yamamoto D. . 1997 Dev. 124: 2671–2681.
Miller MJ, Prigent S, Kupperman E, Rioux L, Park SH, Feramisco JR, White MA, Rutkowski JL and Meinkoth JL. . 1997 J. Biol. Chem. 272: 5600–5605.
Miller DT and Cagan RL. . 1998 Development 125: 2327–2335.
Miyamoto H, Nihonmatsu I, Kondo S, Ueda R, Togashi S, Hirata K, Ikegami Y and Yamamoto D. . 1995 Genes Dev. 9: 612–625.
Murai H, Ikeda M, Kishida S, Ishida O, Okazaki-Kishida M, Matsuura Y and Kikuchi A. . 1997 J. Biol. Chem. 272: 10483–10490.
de Nooij JC and Hariharan IK. . 1995 Science 270: 983–985.
Okazaki M, Kishida S, Hinoi T, Hasegawa T, Tamada M, Kataoka T and Kikuchi A. . 1997 Oncogene 14: 515–521.
Park SH and Weinberg RA. . 1995 Oncogene 11: 2349–2355.
Reichman-Fried M, Dickson B, Hafen E and Shilo BZ. . 1994 Genes Dev. 8: 428–439.
Ridley A and Hall A. . 1992 Cell 70: 389–399.
Robinow S and White K. . 1988 Dev. Biol. 126: 294–303.
Rodriguez-Viciana P, Warne PH, Khwaja A, Marte BM, Pappin D, Das P, Waterfield MD, Ridley A and Downward J. . 1997 Cell 89: 457–467.
Sawamoto K, Okano H, Kobayakawa Y, Hayashi S, Mikoshiba K and Tanimura T. . 1994 Dev. Biol. 164: 267–276.
Sawamoto K, Taguchi A, Hirota Y, Yamada C, Jin M-h and Okano H. . 1998 Cell Death Differ. 5: 262–270.
Simon MA, Bowtell DL, Dodson GS, Laverty TR and Rubin GM. . 1991 Cell 67: 701–716.
Spaargaren M and Bischoff JR. . 1994 Proc. Natl. Acad. Sci. USA 91: 12609–12613.
Strutt ID, Weber U and Mlodzik M. . 1997 Nature 387: 292–295.
Tomlinson A and Ready DF. . 1987 Dev. Biol. 123: 264–275.
Urano T, Emkey R and Feig LA. . 1996 EMBO J. 15: 810–816.
Warrick JM, Paulson HL, Gray-Board GL, Bui QT, Fishbeck KH, Pittman RN and Bonini NM. . 1998 Cell 93: 939–949.
Wassarman DA and Therrien M. . 1997 Adv. Dev. Biol. 5: 1–41.
White MA, Vale T, Camonis JH, Schaefer E and Wigler MH. . 1996 J. Biol. Chem. 271: 16439–16442.
Wolff T and Ready DF. . 1991 Development 113: 825–839.
Wolff T and Ready DF. . 1993 In: The development of Drosophila melanogaster. Bate M and Arias AM. (eds).. Cold Spring Harbor Laboratory Press.
Wolthuis RMF, Bauer B, van't Veer LJ, de Vries-Smits AMM, Cool RH, Spaargaren M, Wittinghofer A, Burgering BMT and Bos JL. . 1996 Oncogene 13: 353–362.
Wolthuis RMF, de Ruiter ND, Cool RH and Bos JL. . 1997 EMBO J. 22: 6748–6761.
Wolthuis RMF, Zwartkruis F, Moen TC and Bos JL. . 1998 Curr. Biol. 8: 471–474.
Zipursky SL and Rubin GM. . 1994 Ann. Rev. Neurosci. 17: 373–397.
Acknowledgements
We thank Kaoru Saigo, Seymor Benzer, Iswar Hariharan, Yuh Nung Jan, Tetsuya Kojima, Liqun Luo, Marek Mlodzik, Rick Fehon, Yasuyoshi Nishida, Gerald Rubin, the Developmental Studies Hybridoma Bank and the Bloomington Stock Center for the fly stocks and antibodies used in this study. We are grateful to Ritsuko Shimamura and Sachiyo Miyao for their help in maintenance of fly strains. This work was supported by grants from the Japan Ministry of Education, Science and Culture to KS, AK and HO.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sawamoto, K., Yamada, C., Kishida, S. et al. Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development. Oncogene 18, 1967–1974 (1999). https://doi.org/10.1038/sj.onc.1202522
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202522