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A ROLE FOR DIACYLGLYCEROL KINASE [gamma] IN TRAFFICKING OUT OF THE trans GOLGI NETWORK

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dc.contributor.authorThorsen, Kevin
dc.contributor.chairBrown, William J.
dc.contributor.committeeMemberEmr, Scott David
dc.contributor.committeeMemberFromme, Joseph Chris
dc.date.accessioned2018-10-03T19:27:06Z
dc.date.available2018-10-03T19:27:06Z
dc.date.issued2017-12-30
dc.description.abstractThe formation of cargo carriers in the secretory pathway occurs primarily through the action of coat proteins (i.e. COPI, COPII and clathrin coats). However, a subset of cargo carriers, primarily membrane tubules, form independently of coat proteins in a process that remains poorly understood. In an siRNA screen of the human kinome, our lab identified diacylglycerol kinase γ (DGKγ) as important in the generation of coat-independent tubular cargo carriers at the Golgi complex and trans Golgi Network (TGN). DGKs converts diacylglycerol (DAG) into phosphatidic acid (PA). Both DAG and PA are signaling lipids known to regulate different steps in trafficking at the Golgi, and a role for DGKs has been anticipated but remains unclear. Here we show that drug- or siRNA-mediated inhibition of DGKγ reduced delivery of a subset of cargoes to the plasma membrane. Inhibition of DGKγ also caused fragmentation of the Golgi complex, a characteristic phenotype of inhibitors of intra Golgi trafficking, as Golgi structure homeostasis depends on continuous membrane tubule formation between cisternae. Furthermore, we found a novel interaction of DGKγ with the regulatory and catalytic subunits of PPP6, as well as the Rab GEF, DENND4C, both of which contribute to trafficking out of the Golgi and may thus suggest a mechanism for DGKγ in this process. Our findings implicate DGKγ as a regulator of trafficking at the Golgi and TGN via a novel role in tubule formation, with several compelling mechanistic possibilities to unravel.
dc.identifier.doihttps://doi.org/10.7298/X4DN438W
dc.identifier.otherThorsen_cornell_0058O_10241
dc.identifier.otherhttp://dissertations.umi.com/cornell:10241
dc.identifier.otherbibid: 10474121
dc.identifier.urihttps://hdl.handle.net/1813/59018
dc.language.isoen_US
dc.subjectCellular biology
dc.subjectBiochemistry
dc.subjectdiacylglycerol kinase
dc.subjectGolgi
dc.subjectsecretion
dc.subjecttubules
dc.subjectMolecular biology
dc.subjectmembrane trafficking
dc.titleA ROLE FOR DIACYLGLYCEROL KINASE [gamma] IN TRAFFICKING OUT OF THE trans GOLGI NETWORK
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineBiochemistry, Molecular and Cell Biology
thesis.degree.grantorCornell University
thesis.degree.levelMaster of Science
thesis.degree.nameM.S., Biochemistry, Molecular and Cell Biology

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