PMID- 10588666
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20191231
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 10
IP  - 12
DP  - 1999 Dec
TI  - The dynamin-like protein DLP1 is essential for normal distribution and morphology
      of the endoplasmic reticulum and mitochondria in mammalian cells.
PG  - 4403-17
AB  - The dynamin family of large GTPases has been implicated in vesicle formation from
      both the plasma membrane and various intracellular membrane compartments. The
      dynamin-like protein DLP1, recently identified in mammalian tissues, has been
      shown to be more closely related to the yeast dynamin proteins Vps1p and Dnm1p
      (42%) than to the mammalian dynamins (37%). Furthermore, DLP1 has been shown to
      associate with punctate vesicles that are in intimate contact with microtubules
      and the endoplasmic reticulum (ER) in mammalian cells. To define the function of 
      DLP1, we have transiently expressed both wild-type and two mutant DLP1 proteins, 
      tagged with green fluorescent protein, in cultured mammalian cells. Point
      mutations in the GTP-binding domain of DLP1 (K38A and D231N) dramatically changed
      its intracellular distribution from punctate vesicular structures to either an
      aggregated or a diffuse pattern. Strikingly, cells expressing DLP1 mutants or
      microinjected with DLP1 antibodies showed a marked reduction in ER fluorescence
      and a significant aggregation and tubulation of mitochondria by
      immunofluorescence microscopy. Consistent with these observations, electron
      microscopy of DLP1 mutant cells revealed a striking and quantitative change in
      the distribution and morphology of mitochondria and the ER. These data support
      very recent studies by other authors implicating DLP1 in the maintenance of
      mitochondrial morphology in both yeast and mammalian cells. Furthermore, this
      study provides the first evidence that a dynamin family member participates in
      the maintenance and distribution of the ER. How DLP1 might participate in the
      biogenesis of two presumably distinct organelle systems is discussed.
FAU - Pitts, K R
AU  - Pitts KR
AD  - Department of Biochemistry and Molecular Biology and Center for Basic Research in
      Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
FAU - Yoon, Y
AU  - Yoon Y
FAU - Krueger, E W
AU  - Krueger EW
FAU - McNiven, M A
AU  - McNiven MA
LA  - eng
GR  - R01 DK044650/DK/NIDDK NIH HHS/United States
GR  - DK44650/DK/NIDDK NIH HHS/United States
GR  - F32 DK009574/DK/NIDDK NIH HHS/United States
GR  - DK09574/DK/NIDDK NIH HHS/United States
GR  - R37 DK044650/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Proteins)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.5 (Dnm1l protein, rat)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Animals
MH  - Cell Compartmentation
MH  - Cells, Cultured
MH  - Dynamins
MH  - Endocytosis/physiology
MH  - Endoplasmic Reticulum/*physiology/ultrastructure
MH  - Fluorescent Antibody Technique
MH  - GTP Phosphohydrolases/*metabolism
MH  - Liver/cytology
MH  - Microscopy, Electron
MH  - *Microtubule-Associated Proteins
MH  - Mitochondria/*physiology/ultrastructure
MH  - Mutation
MH  - Proteins/genetics/*metabolism
MH  - Rats
PMC - PMC25766
EDAT- 1999/12/10 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/12/10 09:00 [entrez]
AID - 10.1091/mbc.10.12.4403 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1999 Dec;10(12):4403-17. doi: 10.1091/mbc.10.12.4403.