title: Phospholipase C-related catalytically inactive protein, a novel microtubule-associated protein 1 light chain 3-binding protein, negatively regulates autophagosome formation.
abstract: Upon starvation, cells undergo autophagy, an intracellular bulk-degradation process, to provide the required nutrients. Here, we observed that phospholipase C-related catalytically inactive protein (PRIP) binds to microtubule-associated protein 1 light chain 3 (LC3), a mammalian autophagy-related initiator that regulates the autophagy pathway. Then, we examined the involvement of PRIP in the nutrient depletion-induced autophagy pathway. Enhanced colocalization of PRIP with LC3 was clearly seen in nutrient-starved mouse embryonic fibroblasts under a fluorescent microscope, and interaction of the proteins was revealed by immunoprecipitation experiments with an anti-LC3 antibody. Under starvation conditions, there were more green fluorescent protein fused-LC3 dots in mouse embryonic fibroblasts from PRIP-deficient mice than in fibroblasts from wild type cells. The formation of new dots in a single cell increased, as assessed by time-lapse microscopy. Furthermore, the increase in autophagosome formation in PRIP-deficient cells was notably inhibited by exogenously overexpressed PRIP. Taken together, PRIP is a novel LC3-binding protein that acts as a negative modulator of autophagosome formation.
authors: Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors: Hisanori
authors: H
authors: Umebayashi
authors: Akiko
authors: A
authors: Mizokami
authors: Miho
authors: M
authors: Matsuda
authors: Kae
authors: K
authors: Harada
authors: Hiroshi
authors: H
authors: Takeuchi
authors: Isei
authors: I
authors: Tanida
authors: Masato
authors: M
authors: Hirata
authors: Takashi
authors: T
authors: Kanematsu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D002384:Catalysis; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010588:Phagosomes; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; C480861:GABARAP protein, mouse; C480860:Map1lc3b protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C496391:Plcl1 protein, mouse; D010738:Type C Phospholipases