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Molecular mechanisms of exocytosis-endocytosis coupling in neuroendocrine cells : role of Scramblase-1 and Oligophrenin-1 proteins

Abstract : Recent studies in neuroendocrine chromaffin cells have suggested that the secretory granule release is temporally and spatially coupled to a compensatory endocytic process. Hence, we hypothesized that the secretory granule membrane would preserve its integrity within the plasma membrane after exocytosis before being retrieved as such along with its components. However, the underlying molecular mechanisms of this compensatory endocytic process are largely unknown today. Therefore my thesis project is aiming to address the following specific question: What are the different mechanisms triggering and regulating exocytosis and the compensatory endocytosis? Physical properties of lipids play fundamental roles in membrane trafficking. They act as a scaffolding system to maintain specific machinery at restricted site of the plasma membrane. For example, the formation of ganglioside- and PIP2-enriched microdomains at the exocytic sites or the phospholipid scrambling across the bilayer plasma membrane, represent attractive processes to fulfill this function during exo- endocytosis events in neuroendocrine cells. Moreover, in view to their important implication in exo-endocytotic processes or lipid remodeling, annexin-A2, synaptotagmin- 1, oligophrenin-1 and phospholipid scramblase-1 have to be considered as potential signal-triggers of the granule endocytosis. During my PhD, I focused in investigating how exocytosis and compensatory endocytosis are regulated by PLSCR-1 and OPHN1 in adrenal chrommaffin cells.
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Catherine Estay Ahumada. Molecular mechanisms of exocytosis-endocytosis coupling in neuroendocrine cells : role of Scramblase-1 and Oligophrenin-1 proteins. Neurobiology. Université de Strasbourg, 2016. English. ⟨NNT : 2016STRAJ088⟩. ⟨tel-01726966⟩

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