HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 34, 35967-35974, August 20, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/34/35967    most recent M404105200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, P.-P. Articles by Blackstone, C. Search for Related Content PubMed PubMed Citation Articles by Zhu, P.-P. Articles by Blackstone, C. Social Bookmarking                      What's this?

Intra- and Intermolecular Domain Interactions of the C-terminal GTPase Effector Domain of the Multimeric Dynamin-like GTPase Drp1^*

Peng-Peng Zhu, Andrew Patterson, Julia Stadler, Daniel P. Seeburg¶, Morgan Sheng¶||, and Craig Blackstone**

From the Cellular Neurology Unit, NINDS, National Institutes of Health and the National Institutes of Health-George Washington University Graduate Partnerships Program in Genetics, National Institutes of Health, Bethesda, Maryland 20892-3704 and the ^¶Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Mammalian Drp1 is a dynamin-like GTPase required for mitochondrial fission. Although it exists primarily as a cytosolic homo-tetramer in vivo, it can also self-assemble into higher order structures on the mitochondrial outer membrane, where it is required for proper mitochondrial division. Functional studies and sequence comparisons have revealed four different structural domains in Drp1, comprising N-terminal GTP-binding, middle, insert B, and C-terminal GTPase effector (GED) domains. Here we describe an intramolecular interaction within Drp1 between the GED and the N-terminal GTP-binding and middle domains. A point mutation (K679A) within the C-terminal GED domain inhibits this intramolecular association, without affecting the formation of Drp1 tetramers or the intermolecular associations among isolated C-terminal domains. Mutant Drp1 K679A exhibits impaired GTPase activity, and when overexpressed in mammalian cells it decreases mitochondrial division. Sedimentation experiments indicate that the K679A mutation either increases Drp1 complex formation or, more likely, decreases complex disassembly as compared with wild-type Drp1. Taken together, these data suggest that the C-terminal GED domain is important for stimulation of GTPase activity, formation and stability of higher order complexes, and efficient mitochondrial division.

Received for publication, April 13, 2004 , and in revised form, June 17, 2004.

^* This work was supported by the intramural program of the NINDS, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Associate Investigator of the Howard Hughes Medical Institute.

^** To whom correspondence should be addressed: Cellular Neurology Unit, NIH, Bldg. 35, Rm. 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704. Tel.: 301-451-9680; Fax: 301-480-4888; E-mail: blackstc{at}ninds.nih.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. J. Tan, M. Husain, C. M. Manlandro, M. Koppenol, A. Z. Fire, and R. B. Hill CED-9 and mitochondrial homeostasis in C. elegans muscle J. Cell Sci., October 15, 2008; 121(20): 3373 - 3382. [Abstract] [Full Text] [PDF]

				X. Wang, B. Su, H. Fujioka, and X. Zhu Dynamin-Like Protein 1 Reduction Underlies Mitochondrial Morphology and Distribution Abnormalities in Fibroblasts from Sporadic Alzheimer's Disease Patients Am. J. Pathol., August 1, 2008; 173(2): 470 - 482. [Abstract] [Full Text] [PDF]

				N. Rismanchi, C. Soderblom, J. Stadler, P.-P. Zhu, and C. Blackstone Atlastin GTPases are required for Golgi apparatus and ER morphogenesis Hum. Mol. Genet., June 1, 2008; 17(11): 1591 - 1604. [Abstract] [Full Text] [PDF]

				M. Bras, V. J. Yuste, G. Roue, S. Barbier, P. Sancho, C. Virely, M. Rubio, S. Baudet, J. E. Esquerda, H. Merle-Beral, et al. Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells Mol. Cell. Biol., October 15, 2007; 27(20): 7073 - 7088. [Abstract] [Full Text] [PDF]

				C.-R. Chang and C. Blackstone Cyclic AMP-dependent Protein Kinase Phosphorylation of Drp1 Regulates Its GTPase Activity and Mitochondrial Morphology J. Biol. Chem., July 27, 2007; 282(30): 21583 - 21587. [Abstract] [Full Text] [PDF]

				S. Wasiak, R. Zunino, and H. M. McBride Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death J. Cell Biol., May 7, 2007; 177(3): 439 - 450. [Abstract] [Full Text] [PDF]

				H. R. Waterham, J. Koster, C. W.T. van Roermund, P. A.W. Mooyer, R. J.A. Wanders, and J. V. Leonard A Lethal Defect of Mitochondrial and Peroxisomal Fission N. Engl. J. Med., April 26, 2007; 356(17): 1736 - 1741. [Abstract] [Full Text] [PDF]

				D. Bhar, M. A. Karren, M. Babst, and J. M. Shaw Dimeric Dnm1-G385D Interacts with Mdv1 on Mitochondria and Can Be Stimulated to Assemble into Fission Complexes Containing Mdv1 and Fis1 J. Biol. Chem., June 23, 2006; 281(25): 17312 - 17320. [Abstract] [Full Text] [PDF]

				P.-P. Zhu, C. Soderblom, J.-H. Tao-Cheng, J. Stadler, and C. Blackstone SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development Hum. Mol. Genet., April 15, 2006; 15(8): 1343 - 1353. [Abstract] [Full Text] [PDF]

				H. Chen and D. C. Chan Emerging functions of mammalian mitochondrial fusion and fission Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R283 - R289. [Abstract] [Full Text] [PDF]

				E. Ingerman, E. M. Perkins, M. Marino, J. A. Mears, J. M. McCaffery, J. E. Hinshaw, and J. Nunnari Dnm1 forms spirals that are structurally tailored to fit mitochondria J. Cell Biol., September 26, 2005; 170(7): 1021 - 1027. [Abstract] [Full Text] [PDF]

				K. R. Pitts, M. A. McNiven, and Y. Yoon Mitochondria-specific Function of the Dynamin Family Protein DLP1 Is Mediated by Its C-terminal Domains J. Biol. Chem., November 26, 2004; 279(48): 50286 - 50294. [Abstract] [Full Text] [PDF]