The dynamin family of mechanoenzymes: pinching in new places

McNiven, Mark A.; Cao, Hong; Pitts, Kelly R.; Yoon, Yisang

doi:10.1016/s0968-0004(99)01538-8

Cited by 324 publications

(252 citation statements)

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“…Examples of the selective inhibition of Tfn uptake by DN Eps15 and LacCer internalization by nystatin are shown in Figures 2, B and C, respectively. In addition, we found that internalization of Tfn, CtxB, and LacCer were each inhibited by ϳ90% in RFs transfected with a DN construct of dynamin (McNiven et al, 2000; Figure 2A). Together, these results demonstrate that in RFs, LacCer internalization occurred by a clathrin-independent mechanism, consistent with our previous studies in HSFs (Puri et al, 2001).…”

Section: Endocytosis Of Multiple Gsl Analogs In Rat Fibroblastsmentioning

confidence: 95%

Selective Caveolin-1–dependent Endocytosis of Glycosphingolipids

Singh

Puri

Valiyaveettil

et al. 2003

MBoC

234

249

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We studied the endocytosis of fluorescent glycosphingolipid (GSL) analogs in various cell types using pathway-specific inhibitors and colocalization studies with endocytic markers and DsRed caveolin-1 (cav-1). Based on inhibitor studies, all GSLs tested were internalized predominantly (Ͼ80%) by a clathrin-independent, caveolar-related mechanism, regardless of cell type. In addition, fluorescent lactosylceramide (LacCer) colocalized with DsRed-cav-1 in vesicular structures upon endocytosis in rat fibroblasts. The internalization mechanism for GSLs was unaffected by varying the carbohydrate headgroup or sphingosine backbone chain length; however, a fluorescent phosphatidylcholine analog was not internalized via caveolae, suggesting that the GSL ceramide core may be important for caveolar uptake. Internalization of fluorescent LacCer was reduced 80 -90% in cell types with low cav-1, but was dramatically stimulated by cav-1 overexpression. However, even in cells with low levels of cav-1, residual LacCer internalization was clathrin independent. In contrast, cholera toxin B subunit (CtxB), which binds endogenous GM 1 , was internalized via clathrin-independent endocytosis in cells with high cav-1 expression, whereas significant clathrin-dependent uptake occurred in cells with low cav-1. Fluorescent GM 1 , normally internalized by clathrin-independent endocytosis in HeLa cells with low cav-1, was induced to partially internalize via the clathrin pathway in the presence of CtxB. These results suggest that GSL analogs are selectively internalized via a caveolar-related mechanism in most cell types, whereas CtxB may undergo "pathway switching" when cav-1 levels are low.

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Section: Endocytosis Of Multiple Gsl Analogs In Rat Fibroblastsmentioning

confidence: 95%

Selective Caveolin-1–dependent Endocytosis of Glycosphingolipids

Singh

Puri

Valiyaveettil

et al. 2003

MBoC

234

249

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“…The multiple cellular functions that have been reported for dynamins would suggest that the different dynamin isoforms and/or splice variants might have different specific functions (McNiven et al, 2000). However, because dynamin is a tetramer (Hinshaw and Schmid, 1995;Ramachandran et al, 2007) …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Because these functions have mostly emerged from studying the effects of overexpression of dominant-negative dynamin mutants, they may reflect indirect or nonspecific effects. Moreover, it is not known whether different dynamin isoforms and/or splice variants participate in distinct membrane-trafficking events (McNiven et al, 2000).Recent studies have also implicated dynamin in cellular processes other than membrane trafficking. For example, dynamin may play significant roles in regulating actin assembly and reorganization via its interactions with many actin-binding proteins Schafer, 2004;Itoh et al, 2005;Kruchten and McNiven, 2006).…”

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confidence: 99%

“…Dyn2 has been localized to the centrosome and its knockdown has been suggested to cause a centrosome cohesion defect in mammalian cells (Thompson et al, 2002;Konopka et al, 2006). The mechanisms guiding these diverse dynamin-mediated processes remain to be established.The multiple cellular functions that have been reported for dynamins would suggest that the different dynamin isoforms and/or splice variants might have different specific functions (McNiven et al, 2000). However, because dynamin is a tetramer (Hinshaw and Schmid, 1995;Ramachandran et al, 2007) …”

mentioning

confidence: 99%

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Isoform and Splice-Variant Specific Functions of Dynamin-2 Revealed by Analysis of Conditional Knock-Out Cells

Liu

Surka

Schroeter

et al. 2008

MBoC

125

163

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Dynamin (Dyn) is a multifunctional GTPase implicated in several cellular events, including endocytosis, intracellular trafficking, cell signaling, and cytokinesis. The mammalian genome encodes three isoforms, Dyn1, Dyn2, and Dyn3, and several splice variants of each, leading to the suggestion that distinct isoforms and/or distinct splice variants might mediate distinct cellular functions. We generated a conditional Dyn2 KO cell line and performed knockout and reconstitution experiments to explore the isoform-and splice variant specific cellular functions of ubiquitously expressed Dyn2. We find that Dyn2 is required for clathrin-mediated endocytosis (CME), p75 export from the Golgi, and PDGFstimulated macropinocytosis and cytokinesis, but not for other endocytic pathways. Surprisingly, CME and p75 exocytosis were efficiently rescued by reintroduction of Dyn2, but not Dyn1, suggesting that these two isoforms function differentially in vesicular trafficking in nonneuronal cells. Both isoforms rescued macropinocytosis and cytokinesis, suggesting that dynamin function in these processes might be mechanistically distinct from its role in CME. Although all four Dyn2 splice variants could equally restore CME, Dyn2ba and -bb were more effective at restoring p75 exocytosis. This splice variant specificity correlated with their differential targeting to the Golgi. These studies reveal isoform and splice-variant specific functions for Dyn2. INTRODUCTIONDynamin (Dyn) is an ϳ100-kDa multidomain GTPase that was first identified as a microtubule binding and bundling protein (Shpetner and Vallee, 1989). Subsequently, dynamin was found to be the mammalian homologue of the Drosophila protein shibire, mutations in which block endocytosis, including synaptic vesicle recycling (Chen et al., 1991;van der Bliek and Meyerowitz, 1991). Dynamin is conserved throughout higher eukaryotes. There is a single gene in Drosophila and Caenorhabditis elegans, but there are three dynamin isoforms in mammals: Dyn1, which is specifically expressed in neurons; Dyn2, which is ubiquitously expressed; and Dyn3, which is mainly expressed in the brain and testes (Urrutia et al., 1997, Ferguson et al., 2007.The best-studied cellular function of dynamin is its involvement in clathrin-mediated endocytosis (CME; Hinshaw, 2000;Sever et al., 2000;Praefcke and McMahon, 2004). However, dynamin has also been implicated in several other membrane-trafficking events including both caveolae-mediated and clathrin-and caveolin-independent endocytic pathways Oh et al., 1998;Lamaze et al., 2001;Pelkmans et al., 2002), phagocytosis (Gold et al., 1999;Yu et al., 2006), macropinocytosis (Schlunck et al., 2004), and trafficking from the trans-Golgi network (TGN; Jones et al., 1998;Kreitzer et al., 2000;Bonazzi et al., 2005). Because these functions have mostly emerged from studying the effects of overexpression of dominant-negative dynamin mutants, they may reflect indirect or nonspecific effects. Moreover, it is not known whether different dynamin isoforms and/or splice varia...

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Dynamin

Palfrey¹,

Brown²

2002

Wiley Encyclopedia of Molecular Medicine

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The dynamin family of mechanoenzymes: pinching in new places

Cited by 324 publications

References 51 publications

Selective Caveolin-1–dependent Endocytosis of Glycosphingolipids

Selective Caveolin-1–dependent Endocytosis of Glycosphingolipids

Isoform and Splice-Variant Specific Functions of Dynamin-2 Revealed by Analysis of Conditional Knock-Out Cells

Dynamin

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