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• W2152254886 endingPage "10539" @default.
• W2152254886 startingPage "10531" @default.
• W2152254886 abstract "Using PC12 cells that express transfected human growth hormone (hGH) as a secreted reporter protein, we have searched for Rab proteins that function in exocytosis. Among the Rab proteins tested, we found that besides the previously described Rab3 proteins, only members of the Rab11 family (Rab11a, 11b, and 25) impaired Ca 2+ -induced exocytosis. Rab11b, which is enriched in brain, had the strongest effect. Consistent with a role in exocytosis, Rab11 and Rab3 proteins were colocalized with other vesicle proteins on secretory vesicles in PC12 cells and on mature synaptic vesicles in brain. Rab11b mutants that fix Rab11b in the GTP- or GDP-bound state both effectively inhibited Ca 2+ -induced exocytosis but seemed to act by distinct mechanisms: whereas GDP-bound Rab11b greatly stimulated constitutive secretion of hGH and depleted hGH stores in secretory vesicles, GTP-bound Rab11b only had a moderate effect on constitutive secretion and no effect on vesicular hGH stores. These results suggest that, consistent with a GTP-dependent regulation of Rab function, GDP-bound Rab11b indirectly inhibits Ca 2+ -triggered exocytosis by causing the loss of hGH from the PC12 cells, whereas GTP-bound Rab11b directly impairs Ca 2+ -triggered exocytosis. In contrast to neuroendocrine PC12 cells in which GTP- and GDP-bound Rab11b inhibited Ca 2+ -induced, but not constitutive, exocytosis, in non-neuronal cells GTP- and GDP-bound Rab11b inhibited constitutive exocytosis and caused an accumulation of cellular hGH. Viewed together, our data suggest that, in addition to other functions, Rab11 has a specific role in neuronal and neuroendocrine but not in non-neuronal cells as a GTP-dependent switch between regulated and constitutive secretory pathways." @default.
• W2152254886 created "2016-06-24" @default.
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• W2152254886 date "2003-11-19" @default.
• W2152254886 modified "2023-10-10" @default.
• W2152254886 title "Divergent Functions of Neuronal Rab11b in Ca²⁺-Regulated versus Constitutive Exocytosis" @default.
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• W2152254886 doi "https://doi.org/10.1523/jneurosci.23-33-10531.2003" @default.
• W2152254886 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6740915" @default.
• W2152254886 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14627637" @default.
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