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Mécanismes de la sécrétion régulée des hormones et des neurotransmetteurs ; rôle des GTPases Rab3 et Rab27.

Abstract : Molecular bases of the calcium-dependent hormone secretion and neurotransmitter release are very similar.
During my PhD work, I focused on various aspects of secretory granules cycle using neuroendocrine cells as a model.
I particularly studied the plasma membrane neurotransmitters transporters´ contribution to the quantal size.
We demonstrated that SERT (Serotonin plasma membrane transporter) over-expression in neuroendocrine PC12 cells increases the size of the release events, and that the control of secretory granules loading is kinetic rather than thermodynamic.
These observations allowed to design a new approach to specifically measure the secretory activity of a transferred subset of cells within a population of PC12 cells.
This method allows to investigate the effect on secretory activity of any protein co-expressed with SERT.
Another part of my work was dedicated to the study of small G proteins Rabs.
These proteins regulate a large number of intercellular traffic pathways. Rab3s play a key role in late steps of neurotransmitters/hormones secretion.
Our results, obtained via electrochemical and biochemical studies, suggest that Rab3s regulate the priming step of the secretory process.
More recently, we focused on MyRIP (Myosin and Rab Interacting Protein) and on Rab27, another Rab family member that is a close relative to Rab3.
We demonstrated that MyRIP is a new Rab27-interacting partner and that both proteins associate with secretory granules. MyRIP also interacts with both myosins 7a/5a and also with actin.
Rab27 and MyRIP are thus able to tether secretory granules to the actin cytoskeleton and to control their mobility in the vicinity of the plasma membrane.
Our studies on Rab3 and Rab27 allowed us to better understand the molecular mechanisms of the process involving these G proteins. They also illustrate the diversity of functions of these proteins.
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https://tel.archives-ouvertes.fr/tel-00011576
Contributor : Jean-Sébastien Schonn <>
Submitted on : Friday, March 10, 2006 - 2:32:00 PM
Last modification on : Wednesday, December 9, 2020 - 3:13:12 PM
Long-term archiving on: : Saturday, April 3, 2010 - 8:54:07 PM

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  • HAL Id : tel-00011576, version 1

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Jean-Sébastien Schonn. Mécanismes de la sécrétion régulée des hormones et des neurotransmetteurs ; rôle des GTPases Rab3 et Rab27.. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2003. Français. ⟨tel-00011576⟩

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