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Dissertation/Thesis Abstract

PI3K Class IIα Is Required for Autophagy
by Karnes, Jonathan Burgess, M.S., Van Andel Research Institute, 2012, 75; 10268645
Abstract (Summary)

Autophagy is a cellular recycling process in which cytoplasmic proteins and organelles are sequestered in a double membrane vesicle, delivered to the lysosome, and degraded following fusion of the two vesicles. A key part of the initiation signaling for autophagy is the generation of phosphoinositol 3-phosphate (P13P) by class III phosphoinositol 3-kinase also knows as Vps 34. In humans there are eight P13K isoforms divided into three classes, four class I enzymes, three class II enzymes, and a single class III enzyme. Of these eight enzymes, only the class III isoform is thought to participate directly in autophagic signaling. A quantitative microscopy based, loss-of-function survey of all eight P13K isoforms was used to determine their relative contribution to autophagic signaling, as measured by LC3 positive autophagic vesicles. As predicted, knockdown of P13K-class III reduced the number of autophagic vesicles in cells. Interestingly, knockdown of the P13K-class IIα isoform had an even more potent effect on reducing the number of autophagic vesicles than knockdown of P13K-class III. In follow up studies, knockdown of P13K-class IIα reduced endogenous LC3 conversion, caused the accumulation of p62 and lipid droplets, and colocalized with endosomal markers. These results suggest P13K-class IIα may act to promote autophagy through the shuttling of endosomal vesicles into the autophagic pathway and approaches to test this hypothesis will be discussed. The requirement of P13K-class IIα for autophagy is an important finding as it indicates a role for class II P13Ks in autophagy.

Indexing (document details)
Advisor: MacKeigan, Jeff
Commitee: Fingar, Diane, Furge, Kyle, Xu, H. Eric
School: Van Andel Research Institute
Department: Biomedical
School Location: United States -- Michigan
Source: MAI 56/05M(E), Masters Abstracts International
Subjects: Molecular biology, Cellular biology, Biochemistry
Publication Number: 10268645
ISBN: 978-1-369-87018-3
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