PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy.
Phosphoinositides regulate a wide range of cellular activities, including membrane trafficking and biogenesis, via interaction with various effector proteins that contain phosphoinositide binding motifs. We show that in the yeast Pichia pastoris, phosphatidylinositol 4'-monophosphate (PI4P) initiates de novo membrane synthesis that is required for peroxisome degradation by selective autophagy and that this PI4P signaling is modulated by an ergosterol-converting PpAtg26 (autophagy-related) protein harboring a novel PI4P binding GRAM (glucosyltransferase, Rab-like GTPase activators, and myotubularins) domain. A phosphatidylinositol-4-OH kinase, PpPik1, is the primary source of PI4P. PI4P concentrated in a protein-lipid nucleation complex recruits PpAtg26 through an interaction with the GRAM domain. Sterol conversion by PpAtg26 at the nucleation complex is necessary for elongation and maturation of the membrane structure. This study reveals the role of the PI4P-signaling pathway in selective autophagy, a process comprising multistep molecular events that lead to the de novo membrane formation.
Yamashita
Shun-ichi
S
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Oku
Masahide
M
Wasada
Yuko
Y
Ano
Yoshitaka
Y
Sakai
Yasuyoshi
Y
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010843:Pichia / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D015398:Signal Transduction / Q000502:physiology*
D020690:GTPase-Activating Proteins; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D005964:Glucosyltransferases; D019870:1-Phosphatidylinositol 4-Kinase; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin