Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis

Sever, Sanja; Muhlberg, Amy B.; Schmid, Sandra L.

doi:10.1038/19024

Cited by 342 publications

(392 citation statements)

References 40 publications

(39 reference statements)

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“…Based on these findings, dynamin's AH domain was renamed the GED [36]. Overproduction of a dynamin GED mutation predicted to prolong the GTP-bound state was shown to enhance the rate of endocytosis in vivo, consistent with the idea that dynamin-GTP regulates a rate-limiting step in endocytosis [36]. A later study established that this rate-limiting step was the formation of constricted coated pits [35].…”

Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 88%

“…Evidence that the GTPase cycle of Dnm1p might regulate this rate-limiting step in mitochondrial fission comes from mutational studies of the Dnm1p AH domain [28]. In previous in vitro studies of mammalian dynamin, the AH domain was shown to stimulate GTP hydrolysis by dynamin after the protein assembled to form higher-order structures [35,36]. Based on these findings, dynamin's AH domain was renamed the GED [36].…”

Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 99%

“…In previous in vitro studies of mammalian dynamin, the AH domain was shown to stimulate GTP hydrolysis by dynamin after the protein assembled to form higher-order structures [35,36]. Based on these findings, dynamin's AH domain was renamed the GED [36]. Overproduction of a dynamin GED mutation predicted to prolong the GTP-bound state was shown to enhance the rate of endocytosis in vivo, consistent with the idea that dynamin-GTP regulates a rate-limiting step in endocytosis [36].…”

Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 99%

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Mitochondrial dynamics and division in budding yeast

Shaw

Nunnari

2002

Trends in Cell Biology

333

297

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Mitochondria adopt a variety of different shapes in eukaryotic cells, ranging from multiple, small compartments to elaborate tubular networks. The establishment and maintenance of different mitochondrial morphologies depends, in part, on the equilibrium between opposing fission and fusion events. Recent studies in yeast, flies, worms and mammalian cells indicate that three highmolecular-weight GTPases control mitochondrial membrane dynamics. One of these is a dynamin-related GTPase that acts on the outer mitochondrial membrane to regulate fission. Recently, genetic approaches in budding yeast have identified additional components of the fission machinery. These and other new findings suggest a common mechanism for membrane fission events that has been conserved and adapted during eukaryotic evolution.Although it is generally accepted that mitochondria play key roles in apoptosis, the cell stress response, aging and various genetically inherited diseases, it is only recently that the regulation of mitochondrial morphology has been recognized as an important factor controlling cell function. It is now known that three conserved GTPases, called Dnm1/Drp1/ Dlp1, Fzo/mitofusin and Mgm1/Opa1/Msp1, regulate mitochondrial fission, fusion and membrane structure in many organisms. Moreover, a recent study demonstrated that inhibition of mammalian Drp1 function blocks cell death, suggesting that mitochondrial fission plays an essential role in apoptosis [1]. This finding raises the possibility that Drp1 (and perhaps Fzo-and Mgm1-type) GTPases are targets of signals that determine how mitochondrial membrane morphology changes in response to intracellular and extracellular cues.A comprehensive list of the genes and proteins implicated in mitochondrial membrane dynamics can be found in several excellent reviews [2][3][4]. Here, we describe what is known about the three GTPases that regulate mitochondrial membrane dynamics and highlight new studies in budding yeast that provide insight into the mechanism of mitochondrial fission. Mitochondrial morphology and membrane dynamicsAlthough the mitochondrion is always surrounded by a double membrane, contains a DNA genome and specializes in the synthesis of ATP, studies using vital dyes and the green fluorescent protein indicate that the morphology of this organelle is different in different cell types and organisms [5][6][7]. In some cells, mitochondria appear as small, bean-shaped compartments dispersed throughout the cytoplasm. In others, the organelles form elongated tubules or a single, highly branched reticulum. Mitochondria continuously grow, divide and fuse throughout the life of a cell and it is the frequency of fission events relative to fusion events that largely determines steady-state organelle morphology. NIH Public Access

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Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 88%

Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 99%

Section: Regulation By Dnm1p Occurs Via a Multistep Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial dynamics and division in budding yeast

Shaw

Nunnari

2002

Trends in Cell Biology

333

297

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“…Dynamin, a large GTPase, forms a collar around membrane invaginations to cause scission of budding vesicles that are targetted to the endocytic membrane system. Dynamin self assembly and GTPase activity are significantly enhanced by microtubules [142][143][144]. Further dynamin has been identified in complex with actin regulators, including profilin and ROCK [145].…”

Section: Microtubule and Endocytic Regulation Of Focal Adhesionsmentioning

confidence: 99%

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

Pullikuth

Catling

2007

Cellular Signalling

135

107

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Cell migration is critical for many physiological processes and is often misregulated in developmental disorders and pathological conditions including cancer and neurodegeneration. MAPK signaling and the Rho family of proteins are known regulators of cell migration that exert their influence on cellular cytoskeleton during cell adhesion and migration. Here we review data supporting the view that localized ERK signaling mediated through recently identified scaffold proteins may regulate cell migration.

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“…It is believed to have a direct role in detaching clathrin-coated vesicles from the plasma membrane [6,7] but it has recently been proposed to have a role as a switch to regulate the endocytic step [8]. So far, at least three different dynamin genes have been found with different expression patterns and possibly different functions.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the mouse dynamin I gene promoter and identification of sequences that direct expression in neuronal cells

Yoo

Lee

Jeong

et al. 2000

Biochemical Journal

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Dynamin I is expressed at high levels in brain and its expression is regulated during the developmental stages of brain. To elucidate the molecular mechanism by which the expression is tissue-specifically regulated, we cloned the 5′-flanking region of the mouse dynamin I gene and determined the nucleotide sequence of 1036 bases upstream from the translation start site. Transient transfection studies with a chloramphenicol acetyltransferase reporter gene in neuroblastoma NS20Y and Lewis lung cells demonstrated that the 5′-flanking region has a cell-type-specific promoter activity. Deletion analyses demonstrated that the minimal promoter activity was detected in the proximal region 195bp upstream of the translation initiation codon (-90 to +105). The minimal promoter was embedded in a GC-rich region (75% GC content), in which an Sp1-binding motif and a nuclear factor (NF)-κB-like element (NE-1) were found, but it lacked TATA and CAAT boxes. Mutational analysis and electrophoretic mobility-shift assay analysis revealed that Sp1 binds to the Sp1 site and that this element is critical for the promoter activity of the dynamin I gene. We found that the NE-1 sequence is required for the expression of the dynamin I gene but NEBP (NE-1-binding protein), which binds to the NE-1 sequence, is not NF-κB. We also found that one base in the NE-1 sequence (the underlined G residue in GGGATTCG̲CGGA) is critical for binding specificity to discriminate between NEBP and NF-κB. By UV cross-linking analysis, we found that NEBP is an approx. 104kDa nuclear protein.

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Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis

Cited by 342 publications

References 40 publications

Mitochondrial dynamics and division in budding yeast

Mitochondrial dynamics and division in budding yeast

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

Characterization of the mouse dynamin I gene promoter and identification of sequences that direct expression in neuronal cells

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