Molecular mechanism of myosin Va recruitment to dense core secretory granules.

Détails

ID Serval
serval:BIB_5CB3F73E9379
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecular mechanism of myosin Va recruitment to dense core secretory granules.
Périodique
Traffic
Auteur(s)
Brozzi F., Diraison F., Lajus S., Rajatileka S., Philips T., Regazzi R., Fukuda M., Verkade P., Molnár E., Váradi A.
ISSN
1600-0854 (Electronic)
ISSN-L
1398-9219
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
13
Numéro
1
Pages
54-69
Langue
anglais
Résumé
The brain-spliced isoform of Myosin Va (BR-MyoVa) plays an important role in the transport of dense core secretory granules (SGs) to the plasma membrane in hormone and neuropeptide-producing cells. The molecular composition of the protein complex that recruits BR-MyoVa to SGs and regulates its function has not been identified to date. We have identified interaction between SG-associated proteins granuphilin-a/b (Gran-a/b), BR-MyoVa and Rab27a, a member of the Rab family of GTPases. Gran-a/b-BR-MyoVa interaction is direct, involves regions downstream of the Rab27-binding domain, and the C-terminal part of Gran-a determines exon specificity. MyoVa and Gran-a/b are partially colocalised on SGs and disruption of Gran-a/b-BR-MyoVa binding results in a perinuclear accumulation of SGs which augments nutrient-stimulated hormone secretion in pancreatic beta-cells. These results indicate the existence of at least another binding partner of BR-MyoVa that was identified as rabphilin-3A (Rph-3A). BR-MyoVa-Rph-3A interaction is also direct and enhanced when secretion is activated. The BR-MyoVa-Rph-3A and BR-MyoVa-Gran-a/b complexes are linked to a different subset of SGs, and simultaneous inhibition of these complexes nearly completely blocks stimulated hormone release. This study demonstrates that multiple binding partners of BR-MyoVa regulate SG transport, and this molecular mechanism is universally used by neuronal, endocrine and neuroendocrine cells.
Mots-clé
dense core secretory granules, granuphilin-a, b, hormone- and neuropeptide-secreting cell, hormone secretion, myosin Va, Rab27, rabphilin-3A, tripartite complex
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/01/2012 11:58
Dernière modification de la notice
20/08/2019 15:15
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