REGULATION OF MACROAUTOPHAGY BY VITAMIN A/ RETINOIDS

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dc.contributor.advisorBossis, Ioannisen_US
dc.contributor.authorRajawat, Yogendra Singhen_US
dc.contributor.departmentVeterinary Medical Scienceen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2013-10-10T05:34:07Z
dc.date.available2013-10-10T05:34:07Z
dc.date.issued2013en_US
dc.description.abstractRetinoic acids (RAs) have diverse biologic effects and regulate several cellular functions. Here, we investigated the role of RA on autophagy by studying its effects on autophagosome (AUT) maturation, as well as on upstream regulators of autophagosome biogenesis. Our studies, based on the use of pH-sensitive fluorescent reporter markers, suggest that RA promotes AUT acidification and maturation. By using competitive inhibitors and specific agonists, we demonstrated that this effect is not mediated by the classic Retinoic Acid Receptor (RAR) and Retinoid X Receptors (RXR). RA did not affect the protein expression levels of upstream regulators of autophagy, such as Beclin-1, phospho-mTOR, and phospho-Akt1, but induced redistribution of both endogenous cation-independent mannose-6-phosphate receptor CI-MPR and transiently transfected GFP and RFP full-length CI-MPR fusion proteins from the trans-Golgi region to acidified AUT structures. Those structures were found to be amphisomes (acidified AUTs) and not autophagolysosomes. The critical role of CI-MPR in AUT maturation was further demonstrated by siRNA-mediated silencing of endogenous CI-MPR. Transient CI-MPR knockdown resulted in remarkable accumulation of nonacidified AUTs, a process that could not be reversed with RA.These results suggest that RA induces AUT acidification and maturation by regulating CI-MPR subcellular location, a process critical in the cellular autophagic mechanism.en_US
dc.identifier.urihttp://hdl.handle.net/1903/14646
dc.subject.pqcontrolledVeterinary medicineen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pquncontrolledAll trans retinoic aciden_US
dc.subject.pquncontrolledAutophagosome maturationen_US
dc.subject.pquncontrolledAutophagyen_US
dc.subject.pquncontrolledCation-independent Mannose-6-Phosphate Receptoren_US
dc.subject.pquncontrolledLC3en_US
dc.subject.pquncontrolledVitamin Aen_US
dc.titleREGULATION OF MACROAUTOPHAGY BY VITAMIN A/ RETINOIDSen_US
dc.typeDissertationen_US

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