@article { , title = {Molecular mechanism of Myosin Va recruitment to dense core secretory granules}, abstract = {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. © 2011 John Wiley \& Sons A/S.}, doi = {10.1111/j.1600-0854.2011.01301.x}, eissn = {1600-0854}, issn = {1398-9219}, issue = {1}, journal = {Traffic}, pages = {54-69}, publicationstatus = {Published}, publisher = {Wiley}, url = {https://uwe-repository.worktribe.com/output/958443}, volume = {13}, keyword = {Centre for Research in Biosciences, Granuphilin-a/b, Rabphilin-3A, Rab27, dense core secretory granules, hormone secretion, myosin Va, tripartite complex, hormone and neuropeptide secreting cell}, year = {2012}, author = {Brozzi, Flora and Diraison, Frederique and Lajus, Sophie and Rajatileka, Shavanthi and Philips, Thomas and Regazzi, Romano and Fukuda, Mitsunori and Verkade, Paul and Molnár, Elek and Varadi, Aniko} }