Src kinase regulates the integrity and function of the Golgi apparatus via activation of dynamin 2
- 15 March 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (13), 5863-5868
- https://doi.org/10.1073/pnas.0915123107
Abstract
The size and integrity of the Golgi apparatus is maintained via a tightly controlled regulation of membrane traffic using a variety of different signaling and cytoskeletal proteins. We have recently observed that activation of c-Src has profound effects on Golgi structure, leading to dramatically vesiculated cisternae in a variety of cell types. As the large GTPase dynamin (Dyn2) has been implicated in Golgi vesiculation during secretion, we tested whether inhibiting Dyn2 activity by expression of a Dyn2K44A mutant or siRNA knockdown could attenuate active Src-induced Golgi fragmentation. Indeed, these perturbations attenuated fragmentation, and expression of a Dyn2Y(231/597)F mutant protein that cannot be phosphorylated by Src kinase had a similar effect . Finally, we find that Dyn2 is markedly phosphorylated during the transit of VSV-G protein through the TGN whereas expression of the Dyn2Y(231/597)F mutant significantly reduces exit of the nascent protein from this compartment. These findings demonstrate that activation of Dyn2 by Src kinase regulates Golgi integrity and vesiculation during the secretory process.Keywords
This publication has 43 references indexed in Scilit:
- LIM Kinase 1 and Cofilin Regulate Actin Filament Population Required for Dynamin-dependent Apical Carrier Fission from theTrans-Golgi NetworkMolecular Biology of the Cell, 2009
- Isoform and Splice-Variant Specific Functions of Dynamin-2 Revealed by Analysis of Conditional Knock-Out CellsMolecular Biology of the Cell, 2008
- Src Signaling Regulates Completion of Abscission in Cytokinesis through ERK/MAPK Activation at the MidbodyPublished by Elsevier BV ,2007
- Golgins and GTPases, giving identity and structure to the Golgi apparatusBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2005
- CtBP3/BARS drives membrane fission in dynamin-independent transport pathwaysNature, 2005
- Mechanism of Constitutive Export from the Golgi: Bulk Flow via the Formation, Protrusion, and En Bloc Cleavage of largetrans-Golgi Network Tubular DomainsMolecular Biology of the Cell, 2003
- Small cargo proteins and large aggregates can traverse the Golgi by a common mechanism without leaving the lumen of cisternaeThe Journal of cell biology, 2001
- Procollagen Traverses the Golgi Stack without Leaving the Lumen of CisternaeCell, 1998
- Dynamin Associates with Src-Homology Collagen (SHC) and Becomes Tyrosine Phosphorylated in Response to InsulinEndocrinology, 1998
- Dynamin-mediated Internalization of CaveolaeThe Journal of cell biology, 1998