![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 12, Issue 9, 2894-2905, September 2001
Center for Basic Research in Digestive Diseases and Department of
Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
55905
Dynamins are large GTPases with mechanochemical properties that are
known to constrict and tubulate membranes. A recently identified
mammalian dynamin-like protein (DLP1) is essential for the proper
cellular distribution of mitochondria and the endoplasmic reticulum in
cultured cells. In this study, we investigated the ability of DLP1 to
remodel membranes similar to conventional dynamin. We found that the
expression of a GTPase-defective mutant, DLP1-K38A, in cultured cells
led to the formation of large cytoplasmic aggregates. Electron
microscopy (EM) of cells expressing DLP1-K38A revealed that these
aggregates were comprised of membrane tubules of a consistent diameter.
High-magnification EM revealed the presence of many regular striations
along individual membrane tubules, and immunogold labeling confirmed
the association of DLP1 with these structures. Biochemical experiments
with the use of recombinant DLP1 and labeled GTP demonstrated that
DLP1-K38A binds but does not hydrolyze or release GTP. Furthermore, the
affinity of DLP1-K38A for membrane is increased compared with wild-type
DLP1. To test whether DLP1 could tubulate membrane in vitro,
recombinant DLP1 was combined with synthetic liposomes and nucleotides.
We found that DLP1 protein alone assembled into sedimentable
macromolecular structures in the presence of
guanosine-5'-O-(3-thio)triphosphate (GTP
S) but not
GTP. EM of the GTPS-treated DLP1 revealed clusters of stacked
helical ring structures. When liposomes were included with DLP1,
formation of long membrane tubules similar in size to those formed in
vivo was observed. Addition of GTPS greatly enhanced membrane tubule
formation, suggesting the GTP-bound form of DLP1 deforms liposomes into
tubules as the DLP1-K38A does in vivo. These results provide the first
evidence that the dynamin family member, DLP1, is able to tubulate
membranes both in living cells and in vitro. Furthermore, these
findings also indicate that despite the limited homology to
conventional dynamins (35%) these proteins remodel membranes in a
similar manner.
This article has been cited by other articles:
|
|
 |
|
  T. Yu, S.-S. Sheu, J. L. Robotham, and Y. Yoon Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species Cardiovasc Res, July 15, 2008; 79(2): 341 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Sung, O. Engmann, M. A. Teylan, A. C. Nairn, P. Greengard, and Y. Kim WAVE1 controls neuronal activity-induced mitochondrial distribution in dendritic spines PNAS, February 26, 2008; 105(8): 3112 - 3116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gehrig, R. B. Cornell, and N. D. Ridgway Expansion of the Nucleoplasmic Reticulum Requires the Coordinated Activity of Lamins and CTP:Phosphocholine Cytidylyltransferase {alpha} Mol. Biol. Cell, January 1, 2008; 19(1): 237 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Karbowski, A. Neutzner, and R. J. Youle The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division J. Cell Biol., October 3, 2007; 178(1): 71 - 84. [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]
|
|
|
|
 |
|
 A.-L. Chanez, A. B. Hehl, M. Engstler, and A. Schneider Ablation of the single dynamin of T. brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest J. Cell Sci., July 15, 2006; 119(14): 2968 - 2974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ren, P. Vajjhala, J. S. Lee, B. Winsor, and A. L. Munn The BAR Domain Proteins: Molding Membranes in Fission, Fusion, and Phagy Microbiol. Mol. Biol. Rev., March 1, 2006; 70(1): 37 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yu, J. L. Robotham, and Y. Yoon Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology PNAS, February 21, 2006; 103(8): 2653 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nguyen, J. Bjorkman, B. C. Paton, and D. I. Crane Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance J. Cell Sci., February 15, 2006; 119(4): 636 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koch, Y. Yoon, N. A. Bonekamp, M. A. McNiven, and M. Schrader A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells Mol. Biol. Cell, November 1, 2005; 16(11): 5077 - 5086. [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]
|
|
|
|
|
|
T. Yu, R. J. Fox, L. S. Burwell, and Y. Yoon Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1 J. Cell Sci., September 15, 2005; 118(18): 4141 - 4151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Neuspiel, R. Zunino, S. Gangaraju, P. Rippstein, and H. McBride Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization J. Biol. Chem., July 1, 2005; 280(26): 25060 - 25070. [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]
|
|
|
|
 |
|
 P. S. Brookes, Y. Yoon, J. L. Robotham, M. W. Anders, and S.-S. Sheu Calcium, ATP, and ROS: a mitochondrial love-hate triangle Am J Physiol Cell Physiol, October 1, 2004; 287(4): C817 - C833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Karbowski, S.-Y. Jeong, and R. J. Youle Endophilin B1 is required for the maintenance of mitochondrial morphology J. Cell Biol., September 27, 2004; 166(7): 1027 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koch, G. Schneider, G. H. Luers, and M. Schrader Peroxisome elongation and constriction but not fission can occur independently of dynamin-like protein 1 J. Cell Sci., September 1, 2004; 117(17): 3995 - 4006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Varadi, L. I. Johnson-Cadwell, V. Cirulli, Y. Yoon, V. J. Allan, and G. A. Rutter Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1 J. Cell Sci., September 1, 2004; 117(19): 4389 - 4400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-P. Zhu, A. Patterson, J. Stadler, D. P. Seeburg, M. Sheng, and C. Blackstone Intra- and Intermolecular Domain Interactions of the C-terminal GTPase Effector Domain of the Multimeric Dynamin-like GTPase Drp1 J. Biol. Chem., August 20, 2004; 279(34): 35967 - 35974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Stojanovski, O. S. Koutsopoulos, K. Okamoto, and M. T. Ryan Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology J. Cell Sci., March 1, 2004; 117(7): 1201 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Jin, H. Bae, S. J. Kim, Y. H. Jin, C.-H. Goh, D. H. Kim, Y. J. Lee, Y. C. Tse, L. Jiang, and I. Hwang The Arabidopsis Dynamin-Like Proteins ADL1C and ADL1E Play a Critical Role in Mitochondrial Morphogenesis PLANT CELL, October 1, 2003; 15(10): 2357 - 2369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Eura, N. Ishihara, S. Yokota, and K. Mihara Two Mitofusin Proteins, Mammalian Homologues of FZO, with Distinct Functions Are Both Required for Mitochondrial Fusion J. Biochem., September 1, 2003; 134(3): 333 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yoon, E. W. Krueger, B. J. Oswald, and M. A. McNiven The Mitochondrial Protein hFis1 Regulates Mitochondrial Fission in Mammalian Cells through an Interaction with the Dynamin-Like Protein DLP1 Mol. Cell. Biol., August 1, 2003; 23(15): 5409 - 5420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hirayama, T. M. Bajari, J. Nimpf, and W. J. Schneider Receptor-Mediated Chicken Oocyte Growth: Differential Expression of Endophilin Isoforms in Developing Follicles Biol Reprod, May 1, 2003; 68(5): 1850 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koch, M. Thiemann, M. Grabenbauer, Y. Yoon, M. A. McNiven, and M. Schrader Dynamin-like Protein 1 Is Involved in Peroxisomal Fission J. Biol. Chem., February 28, 2003; 278(10): 8597 - 8605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Lee, J. B. Jin, J. Song, M. K. Min, D. S. Park, Y.-W. Kim, and I. Hwang The Intermolecular Interaction between the PH Domain and the C-terminal Domain of Arabidopsis Dynamin-like 6 Determines Lipid Binding Specificity J. Biol. Chem., August 23, 2002; 277(35): 31842 - 31849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Accola, B. Huang, A. Al Masri, and M. A. McNiven The Antiviral Dynamin Family Member, MxA, Tubulates Lipids and Localizes to the Smooth Endoplasmic Reticulum J. Biol. Chem., June 7, 2002; 277(24): 21829 - 21835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Fukushima, E. Brisch, B. R. Keegan, W. Bleazard, and J. M. Shaw The GTPase Effector Domain Sequence of the Dnm1p GTPase Regulates Self-Assembly and Controls a Rate-limiting Step in Mitochondrial Fission Mol. Biol. Cell, September 1, 2001; 12(9): 2756 - 2766. [Abstract] [Full Text] [PDF]
|
|
