title: Lysosomal targeting of phafin1 mediated by Rab7 induces autophagosome formation.
abstract: Autophagy orchestrates programmed cell death via crossroads of complex vesicle trafficking including autophagosome and lysosome interaction. Phafin1, an endosome proteins composed of Pleckstrin homology (PH) and Fab1-YotB-Vac1p-EEA1 (FYVE) domain membrane-binding domains, is involved in caspase-independent apoptosis. We report here that the increased expression of phafin1 and its FYVE domain caused the formation of enlarged endosomes. Phafin1 also modulates the membrane density of certain receptors and participates in endocytosis and autophagy processes. The PH-domain of phafin1 is dispensable for lysosomal targeting. Moreover, the tail-domain of phafin1 provides lysosomal targeting signature and the ability to induce autophagy that is mediated by Rab7 signaling. The results suggest that in addition to its role in endosome transport, phafin1 is also involved in lysosomal targeting and autophagosome formation.
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Wen-Jie
authors: WJ
authors: Lin
authors: Chih-Yung
authors: CY
authors: Yang
authors: Li-Li
authors: LL
authors: Li
authors: Yung-Hsiang
authors: YH
authors: Yi
authors: Ke-Wei
authors: KW
authors: Chen
authors: Ying-Chih
authors: YC
authors: Lin
authors: Chin-Chun
authors: CC
authors: Liu
authors: Chi-Hung
authors: CH
authors: Lin
mesh_terms: D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; C508358:PLEKHF1 protein, human; C547687:PLEKHF2 protein, human; D033921:Vesicular Transport Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins