Endocytotic mechanisms in synapses

Jarousse, Nadine; Kelly, Regis B.

doi:10.1016/s0955-0674(00)00237-4

Cited by 74 publications

(72 citation statements)

References 80 publications

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“…The general procedure followed the guidelines of the Restriction Fragment Differential Display system (DisplayPROFILE Kit, Qbiogene, Heidelberg, Germany). First, 500 ng of mRNA were reverse transcribed into complementary DNA using an oligodT 18 NV primer followed by second strand synthesis. The obtained double-strand cDNA was purified through columns of silica-gel (QIAquick PCR Purification Kit, Qiagen, Hilden, Germany) and was then cut by the TaqI restriction enzyme to obtain smaller fragments with cohesive ends.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, IL-1β is able to increase and decrease the rate of endocytosis, an effect that may be linked to NO production by iNOS [16]. The endocytotic machinery is composed of various proteins, which may participate directly or indirectly in the signal pathways of cytokine-mediated beta cell destruction [17,18,19]. On the basis of these results, we propose a novel regulatory principle that might operate in insulin-producing cells exposed to pro-inflammatory cytokines.…”

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confidence: 93%

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Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

et al. 2004

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Aims/hypothesis. Cytokines are important humoral mediators of beta cell destruction in autoimmune diabetes. The aim of this study was to identify novel cytokine-induced genes in insulin-producing RINm5F cells, which may contribute to beta cell death or survival. Methods. A global gene expression profile in cytokine-exposed insulin-producing RINm5F cells was achieved by automated restriction fragment differential display PCR. The expression of selected candidate genes was confirmed by real-time RT-PCR analysis. Results. Exposure of RINm5F cells to IL-1β or to a cytokine mixture (IL-1β, TNF-α, IFN-γ) for 6 h resulted in the differential expression of a functional gene cluster. Apart from the well-known up-regulation of the cytokine-responsive genes iNOS, NF-κB, MnSOD and Hsp70, several genes that belong to the functional cluster of the endocytotic pathway were identified. These endocytotic genes comprised: clathrin, megalin, synaptotagmin and calcineurin, which were up-regulated by IL-1β or the cytokine mixture.In contrast, the expression of the calcineurin inhibitor CAIN and of the GDP/GTP exchange protein Rab3 was down-regulated by cytokines. Other up-regulated cytokine-responsive genes were: agrin, murine adherent macrophage protein mRNA (MAMA) and transport-associated protein (TAP1/MTP), whereas the plasma membrane calcium ATPase (PMCA) 2 and PMCA 3 genes were down-regulated by cytokines. Conclusions/interpretation. Our results indicate that genes of the endocytotic pathway are regulated by pro-inflammatory cytokines. This might affect the density of cytokine receptors at the beta cell surface and concomitantly the sensitivity of the cells to cytokine toxicity. A better understanding of the functional cross-talk between endocytotic and cytokine signalling pathways could further the development of novel strategies to protect pancreatic beta cells against toxic effects of pro-inflammatory cytokines.

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Section: Methodsmentioning

confidence: 99%

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confidence: 93%

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

et al. 2004

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“…This process is achieved by adaptor complexes that recognize and concentrate specific membrane proteins in the donor membranes (Bonifacino and Dell 'Angelica, 1999;Kirchhausen, 1999). PC12 cells have been shown to possess two such adaptor-dependent pathways for the assembly of synaptic vesicles, also known as synaptic-like microvesicles (SLMV) (Shi et al, 1998;de Wit et al, 1999;Jarousse and Kelly, 2001). In one pathway, SLMV are generated from the plasma membrane by a vesiculation mechanism that requires the adaptor AP-2, clathrin, and the GTPase dynamin (Shi et al, 1998).…”

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confidence: 99%

The Zinc Transporter ZnT3 Interacts with AP-3 and It Is Preferentially Targeted to a Distinct Synaptic Vesicle Subpopulation

Salazar

Love

Werner

et al. 2004

MBoC

109

178

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Synaptic vesicles (SV) are generated by two different mechanisms, one AP-2 dependent and one AP-3 dependent. It has been uncertain, however, whether these mechanisms generate SV that differ in molecular composition. We explored this hypothesis by analyzing the targeting of ZnT3 and synaptophysin both to PC12 synaptic-like microvesicles (SLMV) as well as SV isolated from wild-type and AP-3-deficient mocha brains. ZnT3 cytosolic tail interacted selectively with AP-3 in cell-free assays. Accordingly, pharmacological disruption of either AP-2-or AP-3-dependent SLMV biogenesis preferentially reduced synaptophysin or ZnT3 targeting, respectively; suggesting that these antigens were concentrated in different vesicles. As predicted, immuno-isolated SLMV revealed that ZnT3 and synaptophysin were enriched in different vesicle populations. Likewise, morphological and biochemical analyses in hippocampal neurons indicated that these two antigens were also present in distinct but overlapping domains. ZnT3 SV content was reduced in AP-3-deficient neurons, but synaptophysin was not altered in the AP-3 null background. Our evidence indicates that neuroendocrine cells assemble molecularly heterogeneous SV and suggests that this diversity could contribute to the functional variety of synapses. INTRODUCTIONThe molecular diversity in total brain synaptic vesicle (SV) composition is generally presumed to result from differential expression of synaptic vesicle membrane proteins in different brain regions. However, the possibility that synaptic vesicles differ in composition because of different biogenesis mechanisms has not been explored. Different vesiculation pathways could result in molecularly diverse synaptic vesicles. Vesiculation mechanisms are known to produce distinct cargo carriers from a population of donor membranes (Bonifacino and Dell'Angelica, 1999;Springer et al., 1999;Boehm and Bonifacino, 2001). This process is achieved by adaptor complexes that recognize and concentrate specific membrane proteins in the donor membranes (Bonifacino and Dell 'Angelica, 1999;Kirchhausen, 1999). PC12 cells have been shown to possess two such adaptor-dependent pathways for the assembly of synaptic vesicles, also known as synaptic-like microvesicles (SLMV) (Shi et al., 1998;de Wit et al., 1999;Jarousse and Kelly, 2001). In one pathway, SLMV are generated from the plasma membrane by a vesiculation mechanism that requires the adaptor AP-2, clathrin, and the GTPase dynamin (Shi et al., 1998). In the second pathway, SLMV are generated from endosomes by the adaptor complex AP-3 (Faundez et al., 1998;Blumstein et al., 2001) and the GTPase ARF1 (Faundez et al., 1997). In contrast to the plasma membrane pathway, the endosomederived mechanism is highly sensitive to brefeldin A (BFA) (Shi et al., 1998).Phenotypes observed in the AP-3-deficient mocha mouse are consistent with a role for the AP-3-dependent, endosome-derived pathway in neurons (Kantheti et al., 1998). The mocha mossy fibers are devoid of both the synaptic vesiclespecific zinc transpor...

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“…Each action potential releases Ϸ0.5% of the total supply of synaptic vesicles in the terminal (1), and, with some neurons firing at a rate of 50 Hz or greater, synapses would lose the ability to secrete neurotransmitter within seconds if they could not reform and refill synaptic vesicles. Endocytosis is the principal means, and perhaps the only means, by which the used vesicles are recovered and recycled into the releasable vesicle pool (2). Moreover, the rate of endocytosis is tightly coupled to the rate of exocytosis.…”

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confidence: 99%

Synaptotagmin promotes both vesicle fusion and recycling

Schwarz

2004

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

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Endocytotic mechanisms in synapses

Cited by 74 publications

References 80 publications

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

The Zinc Transporter ZnT3 Interacts with AP-3 and It Is Preferentially Targeted to a Distinct Synaptic Vesicle Subpopulation

Synaptotagmin promotes both vesicle fusion and recycling

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