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At least 433 records · Page 24Linked to original sources
PubMed1992

Mitochondrial DNA maintenance in yeast requires a protein containing a region related to the GTP-binding domain of dynamin.

Nuclear gene products replicate and partition mitochondrial DNA (mtDNA) molecules in the yeast Saccharomyces cerevisiae. However, few of the relevant genes have been identified. A mutation that results in temperature-sensitive loss of mtDNA identifies one of these genes, MGM1. Deletion of MGM1 shows that aside from its role in the mitochondrion, the gene has no essential cellular function. The MGM1 protein has a 200-amino-acid region that is highly related to a family of GTP-binding proteins of apparently diverse function that includes the microtubule-binding protein, dynamin D100. The temperature-sensitive strain partitions mtDNA molecules at the restrictive temperature, but a defect in mtDNA synthesis results in a reduction in the number of molecules per cell at each cell division. On the basis of the results of this study, we conclude that cells can partition single mitochondrial genomes, and that when a cell receives a single molecule at division it is able to restore the normal complement of multiple copies.

Amino Acid Sequence↗
PubMed2001

Dynamin, encoded by shibire, is central to cardiac function.

Employing the Drosophila heart, a model system for genetic and molecular investigation of cardiac physiology, we demonstrate here an essential role for the protein dynamin, encoded by the Drosophila gene shibire(ts) (shi(ts)), in maintaining normal heart function. In flies bearing two temperature-sensitive alleles of shi, shi(ts1) and shi(ts2), heartbeat is both slower and less rhythmic than in wild-type animals. Serotonin and norepinephrine, normally cardioacceleratory in wild type, are without effect in flies bearing the shi mutation. Electrocardiogram (EKG) analysis reveals a bigeminal beat in mutant hearts, unlike the single electrical pulse in wild-type. The gene no action potential (temperature sensitive), with previously-described cardiac aberrations similar to those of shi, interacts with shi: shi/shi;nap/nap mutants have almost wild-type heart function. J. Exp. Zool. 289:81-89, 2001.

Animals↗
PubMed2000

Spectrum of autoantibodies against a dynamin-related protein, dymple.

OBJECTIVE: To characterize the clinical features of patients with autoantibodies against dymple, a dynamin-related protein. METHODS: Serum samples from 281 patients with rheumatic diseases were examined. The characteristics of antidymple and antibody-reactive determinants were investigated by immunoblotting with the recombinant dymple antigen, including its deletion mutants, and by immunofluorescence studies with affinity-purified serum. RESULTS: Five serum samples (2%) were found to have antidymple. All of these patients were male, and 4 of them had interstitial pneumonitis. Their sera were considered to mainly recognize the N-terminus of dymple, which contains GTP-binding motifs. CONCLUSION: Dymple, which joins the cytoplasmic autoantigens, could be a marker for a newly recognized subset of connective tissue diseases.

Autoantibodies↗
PubMed1993

The VPS1 protein is a dynamin-like GTPase required for sorting proteins to the yeast vacuole.

VPS1 encodes a 79 kDa protein required for the proper sorting of soluble vacuolar proteins in Saccharomyces cerevisiae. The N-terminal half of Vps1p, which contains a consensus GTP-binding motif, shares extensive homology with a growing family of high molecular mass GTP-binding proteins. Members of this family have been implicated in a number of cellular processes. Vps1p most closely resembles the microtubule-associated protein dynamin. As predicted from the sequence, Vps1p binds and hydrolyses GTP. However, no requirement for microtubules was found for Vps1p function in protein sorting. In subcellular fractionation experiments Vps1p associates with the membrane fraction; the C-terminal half of Vps1p is important for this association. Mutational analysis of VPS1 generated two classes of mutations, dominant negative and recessive. The dominant mutations all mapped to the N-terminal half of the protein. Recessive mutations gave rise to either truncated or unstable proteins. A potential Vps1p-interacting protein (Mvp1p) has been isolated by screening for suppressors of the dominant alleles of VPS1. Taken together these results suggest that Vps1p is a two-domain protein that is part of a multi-subunit protein complex involved in vacuolar protein sorting.

Biological Transport↗
PubMed2005

Continuous opioid agonist treatment dose-dependently regulates mu-opioid receptors and dynamin-2 in mouse spinal cord.

Continuous opioid agonist treatment produces tolerance and in some cases mu opioid receptor (muOR) down-regulation. Previous studies indicate that down-regulation of muOR is more likely with high-efficacy opioid agonists (e.g., etorphine), whereas lower efficacy agonists (e.g., morphine) do not regulate muOR density. It has been suggested that muOR down-regulation may depend upon increases in Dynamin-2 (DYN-2) proteins. Therefore, the present study examined the effect of various infusion doses of etorphine on muOR density, DYN-2 protein, and DYN-2 mRNA abundance in mouse spinal cord. Mice were implanted sc with an osmotic pump that infused etorphine (50-250 microg/kg/day). Controls were implanted with inert placebo pellets. At the end of 7 days, mice were sacrificed, spinal cord removed and processed for radioligand binding, quantitative Western blotting, or RT-PCR assay. Results indicate that etorphine induced dose-dependent regulation of muOR density, DYN-2 proteins, and mRNA abundance in mouse spinal cord. Higher infusion doses significantly down-regulated muOR density, increased DYN-2 protein abundance, and decreased DYN-2 mRNA. Analysis of these results indicated a significant correlation between muOR down-regulation and DYN-2 abundance in mouse spinal cord. Taken together, muOR regulation may depend on changes in DYN-2 abundance induced by high-efficacy opioid agonists in mouse spinal cord.

Analgesics, Opioid↗
PubMed1998

Identification of a fission yeast dynamin-related protein involved in mitochondrial DNA maintenance.

Members of the dynamin-related proteins family have been identified in a wide range of organisms, however their precise functions remain elusive. We have identified a new member of that GTPase family in the fission yeast Schizosaccharomyces pombe. We show that Msp1+ is an essential nuclear gene encoding a 101 kDa protein whose closest homologue is the S. cerevisiae MGM1 gene product. We also report that msp1 conditional loss of function affects the maintenance of mitochondrial DNA and leads to growth arrest associated with respiratory deficiency.

Adenosine Triphosphatases↗
PubMed2002

Regulation of Trypanosoma cruzi invasion of nonphagocytic cells by the endocytically active GTPases dynamin, Rab5, and Rab7.

During invasion of nonphagocytic cells by Trypanosoma cruzi (T. cruzi), host cell lysosomes are recruited to the plasma membrane attachment site followed by lysosomal enzyme secretion. The membrane trafficking events involved in invasion have not been delineated. We demonstrate here that T. cruzi invasion of nonphagocytic cells was completely abolished by overexpression of a dominant negative mutant of dynamin. Likewise, overexpression of a dominant negative mutant of Rab5, the rate-limiting GTPase for endocytosis, resulted in reduced infection rates compared with cells expressing Rab5 wild-type. Moreover, cells expressing the activated mutant of Rab5 experienced higher infection rates. A similar pattern was also observed when Rab7-transfected cells were examined. Confocal microscopy experiments showed that parasites colocalized with green fluorescent protein-Rab5-positive early endosomes after 5 min of invasion. These data clearly indicate that newly forming T. cruzi phagosomes first interact with an early endosomal compartment and subsequently with other late component markers before lysosomal interaction occurs.

Animals↗
PubMed1995

New alleles of mgm1: a gene encoding a protein with a GTP-binding domain related to dynamin.

Three previously described genes that affect baker's yeast (Saccharomyces cerevisiae) mitochondrial DNA (mtDNA) or mitochondrial RNA, tpm2-1, mna1-1, and mgm-1-1, are shown to be alleles of the same gene. This report demonstrates that tpm2-1 does not affect recombination of mtDNA. Therefore, there is no evidence that this dynamin-like protein is involved in movement of mtDNA within a cell.

Alleles↗
PubMed1996

Dynamin and receptor-mediated endocytosis.

The internalization of receptor-bound ligands involves concentration of cell surface receptors in specialized areas of the plasma membrane and subsequent formation of clathrin-coated vesicles. The complex process of invagination, constriction and budding of clathrin-coated vesicles employs the coordinated actions of several proteins. This review is focused on the GTPase dynamin, which plays a key role in the constriction of coated pits.

Animals↗
PubMed1989

Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules.

We report that calf brain microtubules prepared without nucleotide contain, in addition to kinesin and dynein, a polypeptide of 100 kd that could be dissociated by nucleotide. The protein was selectively extracted from microtubules using a combination of GTP and AMP-PNP. The extract contained microtubule-stimulated (6-fold) MgATPase activity that partitioned into two components upon further purification: the 100 kd polypeptide and a soluble activating fraction. The 100 kd protein induced microtubules to form hexagonally packed bundles containing periodic cross bridges spaced 13 nm apart. In the presence of ATP and the activating fraction, bundles fragmented, elongated, and exhibited other behavior indicative of sliding between microtubules. These findings indicate that the 100 kd protein is part of a novel mechanochemical enzyme, which we term "dynamin", that may mediate microtubule sliding in vivo.

Adenosine Triphosphatases↗
PubMed1994

Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin.

The X-ray crystal structure of the pleckstrin homology (PH) domain from human dynamin has been refined to 2.2 A resolution. A seven-stranded beta sandwich of two orthogonal antiparallel beta sheets is closed at one corner by a C-terminal alpha helix. Opposite this helix are the three loops that vary most among PH domains. The basic fold is very similar to that of two other PH domains recently determined by nuclear magnetic resonance, confirming that PH domain with known structure is electrostatically polarized, with the three variable loops forming a positively charged surface. This surface includes the position of the X-linked immunodeficiency mutation in the Btk PH domain and may serve as a ligand-binding surface.

Amino Acid Sequence↗
PubMed1995

Phosphorylation of synapsin I and dynamin in rat forebrain synaptosomes: modulation by sigma (sigma) ligands.

The effects of sigma (sigma) ligands on protein phosphorylation were examined in crude, rat forebrain synaptosomes. Synaptosomes were prelabelled with 32P(i) and incubated with the sigma ligands 1,3-di-o-tolylguanidine (DTG), (+)pentazocine and (-)pentazocine (3, 10, 30, 100, 300 microM), or haloperidol, reduced haloperidol, and (+)SKF 10,047 (100 microM). Aliquots were then incubated for 10 s in control (5 mM K+) or depolarising buffer (41 mM K+). All the sigma ligands increased basal phosphorylation of synapsin Ib and other proteins including dynamin, and inhibited the depolarisation-dependent increase in phosphorylation of synapsin Ib in synaptosomes. The effects of these ligands are not directly on protein kinases or protein phosphatases. This indicates that the sigma ligands are mediating their effects via interaction with sigma binding sites, and suggest, for the first time, that protein phosphorylation may be one mechanism through which sigma ligands produce their biological effects.

Animals↗
PubMed1994

The role of clathrin, adaptors and dynamin in endocytosis.

Clathrin-coated vesicles bud from the plasma membrane and from the trans-Golgi network; both populations of coated vesicles participate in the endocytic pathway. Coated-vesicle formation is initiated by the binding of cytosolic adaptor complexes to putative adaptor receptors on the appropriate membrane. Clathrin then binds to the adaptors and assembles to form a coated bud, which pinches off as a coated vesicle. The GTPase dynamin facilitates the formation of coated vesicles at the plasma membrane through an as yet unknown mechanism. Recent studies suggest that regulatory mechanisms may operate at each of these stages.

Adaptation, Physiological↗
PubMed2004

Genomic organization, alternative splicing, and promoter analysis of human dynamin-like protein gene.

The human dynamin-like protein, HdynIV, has recently been cloned and shown to be involved in the formation and trafficking of coated vesicles. In particular, one of the HdynIV variant overexpressions has been suggested to contribute to the pathogenesis of brain tumors. In this paper, we report on the genomic organization of the human HdynIV gene. The gene was found to correspond to 20 exons of genomic sequence on human chromosome 12, distributed over 64kb of genomic DNA. The two exons, numbers 15 and 16, are subjected to differential splicing, generating four different transcripts of a perfect match to our recent report on the four different spliced HdynIV variants [DNA Cell Biol. 19 (2000) 189]. We have also characterized the 5(') regulatory region of the HdynIV gene in order to understand the molecular mechanisms regulating its expression. The transcriptional initiation site was identified by 5(')-RACE. The 5(')-flanking sequence of the HdynIV gene contains three GC boxes that concatenate Ap2- and Sp1-binding motifs, but that does not contain either the TATA or CAAT consensus sequence. A region between -140 and +92 contributed to high promoter activity. Deletion analysis demonstrated that the minimal promoter activity required the region of -110 to -100. Electrophoretic mobility shift assay demonstrated that a putative transcriptional factor bound to the region of -119 to -90. Site-directed mutagenesis analysis of this region revealed that nucleotides at -108 to -100 were essential for transactivation mediated by this transcriptional factor. In conclusion, we have characterized the minimal HdynIV promoter and shown that CTCCCAGCA (-108 to -100) sequence may act as a novel transcriptional element for regulating HdynIV gene expression.

Alternative Splicing↗
PubMed2004

Isolation and functional characterization of a dynamin-like gene from Plasmodium falciparum.

A novel dynamin-like GTPase gene, Pfdyn1, was cloned from an asexual stage cDNA library of Plasmodium falciparum Dd2 strain. Pfdyn1 contains a highly conserved N-terminal tripartite GTPase domain, a coiled-coil region, and a C-terminal 129 aa unknown function domain. Like yeast Vps1p, it lacks pleckstrin homology domain and proline-rich region. Western blot analysis showed that Pfdyn1 is a Triton X-100 insoluble protein expressed only in the mature sub-stage. Morphological studies indicated that Pfdyn1 is partly co-localized with PfGRP, a known ER-resident protein, and localizes diffusely with several membrane structures and a 60-100 nm vesicle both inside and on surface of the parasites and also in the cytoplasm of infected erythrocytes. The dsRNA originated by C-terminus fragment of Pfdyn1 inhibits markedly the growth of P. falciparum parasite at the erythrocyte stage. Those data showed that Pfdyn1 is a conservative, membrane related protein and plays an essential role for the survival of Plasmodium parasite.

Amino Acid Sequence↗
PubMed2005

Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission.

Mitochondria display a variety of shapes, ranging from small and spherical or the classical tubular shape to extended networks. Shape transitions occur frequently and include fusion, fission, and branching. It was reported that some mitochondrial shape transitions are developmentally regulated, whereas others were linked to disease or apoptosis. However, if and how mitochondrial function controls mitochondrial shape through regulation of mitochondrial fission and fusion is unclear. Here, we show that inhibitors of electron transport, ATP synthase, or the permeability transition pore (mtPTP) induced reversible mitochondrial fission. Mitochondrial fission depended on dynamin-related protein 1 (DRP1) and F-actin: Disruption of F-actin attenuated fission and recruitment of DRP1 to mitochondria. In contrast, uncoupling of electron transport and oxidative phosphorylation caused mitochondria to adopt a distinct disk shape. This shape change was independent of the cytoskeleton and DRP1 and was most likely caused by swelling. Thus, disruption of mitochondrial function rapidly and reversibly altered mitochondrial shape either by activation of DRP1-dependent fission or by swelling, indicating a close relationship between mitochondrial fission, shape, and function. Furthermore, our results suggest that the actin cytoskeleton is involved in mitochondrial fission by facilitating mitochondrial recruitment of DRP1.

Actins↗
PubMed2002

The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space.

Mutations in the OPA1 gene are associated with autosomal dominant optic atrophy. OPA1 encodes a dynamin-related protein orthologous to Msp1 of Schizosaccharomyces pombe and Mgm1p of Saccharomyces cerevisiae, both involved in mitochondrial morphology and genome maintenance. We present immuno-fluorescence and biochemical evidences showing that OPA1 resides in the mitochondria where it is imported through its highly basic amino-terminal extension. Proteolysis experiments indicate that OPA1 is present in the inter-membrane space and electron microscopy further localizes it close to the cristae. The strong association of OPA1 with membranes suggests its anchoring to the inner membrane.

3T3 Cells↗
PubMed1999

Interaction between the fission yeast nim1/cdr1 protein kinase and a dynamin-related protein.

The nim1/cdr1 protein kinase is required for an efficient adaptation of cell cycle parameters to changes in nutritional conditions. We have isolated msp1, a new fission yeast member of the dynamin-related large GTPase family, in a two-hybrid screen designed to identify proteins interacting with the nim1 kinase. Msp1 has been shown to be essential for the maintenance of mtDNA and hence for the inheritance of functional mitochondria. We present evidence indicating that niml and mspl proteins physically interact both in vitro and in vivo in fission yeast. These interactions occur through the amino-terminal catalytic domain of nim1 and the carboxy-terminal putative regulatory domain of mspl. These results provide new evidence for the existence of a connection between mitochondrial function and the cell cycle machinery.

Cell Cycle↗