This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Martinu, L.
Right arrow Articles by Chou, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martinu, L.
Right arrow Articles by Chou, M. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2004, p. 9752-9762, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9752-9762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The TBC (Tre-2/Bub2/Cdc16) Domain Protein TRE17 Regulates Plasma Membrane-Endosomal Trafficking through Activation of Arf6{dagger}

Lenka Martinu,1 Jeffrey M. Masuda-Robens ,1,{ddagger},§ Sarah E. Robertson,1,{ddagger} Lorraine C. Santy,2 James E. Casanova,2 and Margaret M. Chou1*

Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,1 Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia2

Received 21 April 2004/ Returned for modification 8 June 2004/ Accepted 17 August 2004

TBC (Tre-2/Bub2/Cdc16) domains are predicted to encode GTPase-activating proteins (GAPs) for Rab family G proteins. While approximately 50 TBC proteins are predicted to exist in humans, little is known about their substrate specificity. Here we show that TRE17 (also called Tre-2 and USP6), a founding member of the TBC family, targets the Arf family GTPase Arf6, which regulates plasma membrane-endosome trafficking. Surprisingly, TRE17 does not function as a GAP for Arf6 but rather promotes its activation in vivo. TRE17 associates directly with Arf6 in its GDP- but not GTP-bound state. Mapping experiments pinpoint the site of interaction to the TBC domain of TRE17. Forced expression of TRE17 promotes the localization of Arf6 to the plasma membrane, leading to Arf6 activation, presumably due to facilitated access to membrane-associated guanine nucleotide exchange factors (GEFs). Furthermore, TRE17 cooperates with Arf6 GEFs to induce GTP loading of Arf6 in vivo. Finally, short interfering RNA-mediated loss of TRE17 leads to attenuated Arf6 activation. These studies identify TRE17 as a novel regulator of the Arf6-regulated plasma membrane recycling system and reveal an unexpected function for TBC domains.

* Corresponding author. Mailing address: University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, 421 Curie Blvd., BRBII Room 1011, Philadelphia, PA 19104-6160. Phone: (215) 573-4126. Fax: (215) 898-9871. E-mail: mmc{at}mail.med.upenn.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org.

{ddagger} J.M.M.-R. and S.E.R. contributed equally to this work.

§ Present address: Glaxo-IMCB Group Institute for Molecular and Cell Biology, Singapore 117609, Singapore.

Molecular and Cellular Biology, November 2004, p. 9752-9762, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.9752-9762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wainszelbaum, M. J., Charron, A. J., Kong, C., Kirkpatrick, D. S., Srikanth, P., Barbieri, M. A., Gygi, S. P., Stahl, P. D. (2008). The Hominoid-specific Oncogene TBC1D3 Activates Ras and Modulates Epidermal Growth Factor Receptor Signaling and Trafficking. J. Biol. Chem. 283: 13233-13242 [Abstract] [Full Text]  
  • Frittoli, E., Palamidessi, A., Pizzigoni, A., Lanzetti, L., Garre, M., Troglio, F., Troilo, A., Fukuda, M., Di Fiore, P. P., Scita, G., Confalonieri, S. (2008). The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway. Mol. Biol. Cell 19: 1304-1316 [Abstract] [Full Text]  
  • Hanono, A., Garbett, D., Reczek, D., Chambers, D. N., Bretscher, A. (2006). EPI64 regulates microvillar subdomains and structure. JCB 175: 803-813 [Abstract] [Full Text]  
  • Klein, S., Franco, M., Chardin, P., Luton, F. (2006). Role of the Arf6 GDP/GTP Cycle and Arf6 GTPase-activating Proteins in Actin Remodeling and Intracellular Transport. J. Biol. Chem. 281: 12352-12361 [Abstract] [Full Text]  
  • Robertson, S. E., Setty, S. R. G., Sitaram, A., Marks, M. S., Lewis, R. E., Chou, M. M. (2006). Extracellular Signal-regulated Kinase Regulates Clathrin-independent Endosomal Trafficking. Mol. Biol. Cell 17: 645-657 [Abstract] [Full Text]  
  • Oliveira, A. M., Chou, M. M., Perez-Atayde, A. R., Rosenberg, A. E. (2006). Aneurysmal Bone Cyst: A Neoplasm Driven by Upregulation of the USP6 Oncogene. JCO 24: e1-e1 [Full Text]  
  • Shen, C., Ye, Y., Robertson, S. E., Lau, A. W., Mak, D.-O. D., Chou, M. M. (2005). Calcium/Calmodulin Regulates Ubiquitination of the Ubiquitin-specific Protease TRE17/USP6. J. Biol. Chem. 280: 35967-35973 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»