Molecular regulation of peptide and neurotransmitter secretion in neuroendocrine cells
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1
University of Cordoba/IMIBIC/CIBERobn, Dept. of Cell Biology, Physiology, and Immunology, Spain
Rab proteins control vesicle trafficking by regulating components of the transport machinery. Particularly, we have shown that Rab18 inhibits secretory granule movement, but the molecular mechanisms involved and the identity of Rab18 effectors remain unknown. We will discuss our recent data on the analysis of the motility of Rab18-associated granules in response to the activation of the secretory pathway, the relationship between Rab18 granules and the microtubule network, as well as on the identification of Rab18 effectors. Specifically, video-microscopy studies in PC12 cells cotransfected with expression vectors coding for the granule marker NPY and for Rab18, revealed that secretory granules, either containing or not Rab18, exhibited similar saltatory movements, including anterograde and retrograde net movements, under basal conditions. However, upon K+ stimulation the percentage of NPY granules moving anterogradely increased, whereas the number of anterograde Rab18 granules decreased. We also found a close spatial relationship between Rab18-bearing granules and microtubules, which was impaired after microtubule depolymerization by nocodazole. Inasmuch as Rab18 modified granule transport dynamics, we investigated the relationship between this GTPase and components of the microtubule-based transport machinery. Thus, FRET experiments showed that Rab18 interacts with kinesin-1 light chain in its active form (after K+ treatment or using a constitutive active Rab18 mutant) and with huntingtin in its inactive conformation, supporting the view that Rab18 impairs the transport of secretory granules by regulating the activity of these microtubule-associated proteins. Finally, by using the yeast two-hybrid system, we have identified additional, novel Rab18 interacting proteins that likely contribute to the effect of this GTPase on granule traffic dynamics. In all, our data has enabled to unveil the underlying molecular mechanisms by which Rab18 controls vesicle traffic in neuroendocrine cells.
Acknowledgements
Acknowledgements: Research relating to this abstract was funded by MINECO/FEDER (BFU2010-17116), J. Andalucía/FEDER (CTS-6606), and CIBERobn (Instituto de Salud Carlos III), Spain.
Keywords:
Rab proteins,
Cytoskeleton,
Neurosecretion,
intracellular traffic,
FRET,
Interactome
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Malagón
MM,
Almabouada
F,
Rabanal
Y and
Vazquez-Martinez
R
(2013). Molecular regulation of peptide and neurotransmitter secretion in neuroendocrine cells.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00047
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Received:
28 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Dr. María M Malagón, University of Cordoba/IMIBIC/CIBERobn, Dept. of Cell Biology, Physiology, and Immunology, Cordoba, 14014, Spain, bc1mapom@uco.es