The phox homology domain of phospholipase D activates dynamin GTPase activity and accelerates EGFR endocytosis

Lee, Chang S.; Kim, Il S.; Park, Jong B.; Lee, Mi N.; Lee, Hye Y.; Suh, Pann‐Ghill; Ryu, Sung Ho

doi:10.1038/ncb1401

Cited by 118 publications

(86 citation statements)

References 30 publications

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“…PLD hydrolyzes phosphatidylcholine to generate PA, which is a cone-shaped lipid that favors membranes with negative curvature and can affect vesicle budding and membrane fission (Donaldson, 2009). The enzymatic activity of PLD is stimulated by ARFs (Cockcroft et al, 1994;Sung et al, 1999); PLD also interacts with dynamin and stimulates its GTPase activity (Lee et al, 2006). Thus, PLD can participate in vesicle budding and membrane fission by producing PA, as well as by stimulating the GTPase activity of dynamin.…”

Section: Discussionmentioning

confidence: 99%

ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

Kondo

Hanai

Nakai

et al. 2012

Cell Struct. Funct.

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ABSTRACT. Small GTPases ARF1 and ARF3 localize mainly to the Golgi apparatus, where they trigger formation of coated carrier vesicles. We previously showed that BIG2, a guanine nucleotide exchange factor specific for ARF1 and ARF3, localizes not only to the trans-Golgi network (TGN) but also to recycling endosomes, where it is involved in regulating the integrity of recycling endosomes. However, it is not yet clear whether ARF1 and ARF3 act downstream of BIG2 to ensure endosome integrity. In this study, we show that EGFP-tagged ARF1 and ARF3 localize to endosomal compartments containing endocytosed transferrin. We further demonstrate that simultaneous depletion of ARF1 and ARF3 induces tubulation of recycling endosomal compartments positive for transferrin receptor, Rab4, and Rab11, but does not significantly affect the integrity of the Golgi apparatus or early or late endosomes. Moreover, the simultaneous depletion of ARF1 and ARF3 suppresses recycling of transferrin but does not affect either its endocytosis or the retrograde transport of TGN38 from early/recycling endosomes to the TGN. In addition, depletion of ARF1 and ARF3 does not affect retrograde transport of CD4-furin from late endosomes to the TGN, or of endocytosed EGF from late endosomes to lysosomes. These results indicate that ARF1 and ARF3 are redundantly required for the integrity of recycling endosomes, and that they regulate transferrin recycling from endosomes to the plasma membrane, but not retrograde transport from endosomal compartments to the TGN.

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Section: Discussionmentioning

confidence: 99%

ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

Kondo

Hanai

Nakai

et al. 2012

Cell Struct. Funct.

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“…However, the upstream event of nanoparticle entry to the cellular compartment and the molecular machinery that drives the dynamics of the internalization to cancer cells is not known. Evidence suggests an important role of dyn-2 in many cellular processes such as EGFR and other receptor endocytosis (28,29,31). EGF stimulated EGFRs have been found to involve both clathrin-dependent and independent pathways (32).…”

Section: Discussionmentioning

confidence: 99%

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

Bhattacharyya¹,

Bhattacharya²,

Curley

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

124

123

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Treatment with monoclonal antibody (mAbs) is a viable therapeutic option in cancer. Recently, these mAbs such as cetuximab, herceptin, etc., have been used as targeting agents to selectively deliver chemotherapeutics to cancerous cells. However, mechanisms of nanoparticles-mAbs interactions with the target cells and its effect on intracellular trafficking and mechanism are currently unknown. In this paper, we demonstrate that the distinct patterning and dynamics of anti-EGFR (epidermal growth factor receptor) antibody cetuximab (C225)-induced EGFR internalization in pancreatic cancer cells with variable receptor expression is altered upon nanoconjugation. Nanoconjugation uniformly enhanced C225-induced EGFR endocytosis in PANC-1, AsPC-1, and MiaPaca-2 cells, influenced its compartmentalization and regulated the involvement of dynamin-2 in the endocytic processes. Receptor endocytosis and its intracellular trafficking were monitored by confocal microscopy and transmission electron microscopy. The role of dynamin-2 in EGFR endocytosis was determined after overexpressing either wild-type dynamin-2 or mutant dynamin-2 in pancreatic cancer cells followed by tracking the receptor-antibody complex internalization by confocal microscopy. Significantly, these findings demonstrate that the nanoconjugation cannot be construed as an innocuous reaction involved in attaching the targeting agent to the nanoparticle, instead it may distinctly alter the cellular processes at the molecular level, at least antibody induced receptor endocytosis. This information is critical for successful design of a nanoparticle-based targeted drug delivery system for future clinical translation.EGFR | nanoparticle | dynamin | pancreatic cancer N anotechnology provides opportunities for biomedical applications that may improve human health care in the future (1-13). Engineered nanoparticles are evolving as promising candidates for various biological applications due to their tunable biophysical and biochemical properties (14-16). However, fundamental studies to understand the mechanism of cell-nanomaterial interactions are still lacking. To advance the successful development of biomedical nanotechnology for clinical use, vivid understanding of such mechanisms is essential.Epidermal growth factor receptor (EGFR) represents a unique target as over expression of EGFR has been implicated in the pathogenesis of many cancers (17, 18). Cetuximab (C225), a monoclonal anti-EGFR antibody, has been approved by the FDA for treatment of colon and head and neck cancers (19). Cetuximab is also in different phases of clinical trials for other cancers (20,21). However, the mechanism and pattern of C225 induced endocytosis of EGFR in pancreatic cancer cells of variable EGFR expression is not fully understood (20,21). Furthermore, the effect of nanoconjugation on the mechanism of C225 induced endocytosis remains to be investigated. Here, we demonstrate the mechanism and endocytic pattern of C225 and gold conjugated-C225 induced internalization of EGFR in pancreatic ...

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“…BARS-dependent membrane fission requires long-chain acylCoAs and it was originally proposed to form PA by adding an acyl chain to lypophosphatidic acid (Weigert et al, 1999; see also Gallop et al, 2005). Alternatively, BARS may collaborate with lipid enzymes such as PLD, whose activity is required for numerous fission and membrane dynamics events (Tuscher et al, 1997;Roth et al, 1999;Freyberg et al, 2003;Pathre et al, 2003;Lee et al, 2006). Like DAG, PA has special biophysical properties, and recent data indicate that PA could act as a docking site for interfacial insertion of positively charged membrane protein domains (Kooijman et al, 2003(Kooijman et al, , 2007, which with a PA-DAG interconversion cycle could be crucial for final membrane constriction/fission of coated/noncoated transport vesicles.…”

Section: Introductionmentioning

confidence: 99%

Diacylglycerol Is Required for the Formation of COPI Vesicles in the Golgi-to-ER Transport Pathway

Fernández-Ulibarri

Vilella

Lázaro‐Diéguez

et al. 2007

MBoC

103

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Diacylglycerol is necessary for trans-Golgi network (TGN) to cell surface transport, but its functional relevance in the early secretory pathway is unclear. Although depletion of diacylglycerol did not affect ER-to-Golgi transport, it led to a redistribution of the KDEL receptor to the Golgi, indicating that Golgi-to-ER transport was perturbed. Electron microscopy revealed an accumulation of COPI-coated membrane profiles close to the Golgi cisternae. Electron tomography showed that the majority of these membrane profiles originate from coated buds, indicating a block in membrane fission. Under these conditions the Golgi-associated pool of ARFGAP1 was reduced, but there was no effect on the binding of coatomer or the membrane fission protein CtBP3/BARS to the Golgi. The addition of 1,2-dioctanoyl-sn-glycerol or the diacylglycerol analogue phorbol 12,13-dibutyrate reversed the effects of endogenous diacylglycerol depletion. Our findings implicate diacylglycerol in the retrograde transport of proteins from Golgi to the ER and suggest that it plays a critical role at a late stage of COPI vesicle formation. INTRODUCTIONRecent observations from several laboratories indicate that membrane lipids regulate intracellular membrane transport, particularly in distal stages of the secretory pathway. Diacylglycerol (DAG) is a simple and small sized signal-transducing lipid which among other functions is necessary for protein transport from the Golgi complex to the cell surface both in yeast and in mammals. Thus, in budding yeast phosphatidylinositol (PI)-transfer Sec14p protein directly regulates DAG homeostasis in the Golgi complex and protein secretion (Bankaitis et al., 1990;Kearns et al., 1997;Huijbregts et al., 2000). In mammals, the reduction of DAG levels at the Golgi caused by the depletion of Nir2 (a peripheral Golgi protein containing a PI-transfer domain) inhibits post-Golgi protein transport (Litvak et al., 2005). DAG acts in the trans-Golgi network (TGN) as a membrane acceptor for specific proteins such as the protein kinase C (PKC) family member PKD/ PKC (Prestle et al., 1996;Liljedahl et al., 2001;Baron andMalhotra, 2002), and Hmun13 (Speight andSilverman, 2005).PKD together with PKC, the trimeric G-protein subunits ␤/␥ (Díaz Anel and Malhotra, 2005), and phosphatidylinositol-4 kinase III␤ (Hausser et al., 2005) directly participate in the post-Golgi transport of plasma membrane proteins containing basolateral sorting information (Yeaman et al., 2004). On the other hand, Hmun13, through the recruitment of Rab34, participates in the Golgi-lysosome protein trafficking (Speight and Silverman, 2005). DAG also promotes the Golgi membrane targeting and activation of other C1 domain-containing signaling molecules such as other PKC isoforms (PKC, PKC, and PKC␦;Maissel et al., 2006;Lehel et al., 1995; Wang et al., 1999, respectively) and Ras guanosine nucleotide-releasing proteins (RasGRPs;Caloca et al., 2003), whose potential involvement in Golgi-associated transport functions remains unexplored.The aforementioned Go...

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The phox homology domain of phospholipase D activates dynamin GTPase activity and accelerates EGFR endocytosis

Cited by 118 publications

References 30 publications

ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis

Diacylglycerol Is Required for the Formation of COPI Vesicles in the Golgi-to-ER Transport Pathway

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