The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells

K. R. Pitts, Yisang Yoon, E. W. Krueger, M. A. McNiven

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224 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4403-4417
Number of pages15
JournalMolecular Biology of the Cell
Volume10
Issue number12
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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Dynamins
Normal Distribution
Endoplasmic Reticulum
Mitochondria
Proteins
Maintenance
Intracellular Membranes
Fungal Proteins
GTP Phosphohydrolases
Mutant Proteins
Guanosine Triphosphate
Green Fluorescent Proteins
Fluorescence Microscopy
Point Mutation
Microtubules
Organelles
Cultured Cells
Electron Microscopy
Yeasts
Fluorescence

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. / Pitts, K. R.; Yoon, Yisang; Krueger, E. W.; McNiven, M. A.

In: Molecular Biology of the Cell, Vol. 10, No. 12, 01.01.1999, p. 4403-4417.

Research output: Contribution to journalArticle

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