title: SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation.
abstract: Mouse SKD1 AAA ATPase is involved in the sorting and transport from endosomes; cells overexpressing a dominant-negative mutant, SKD1(E235Q) were defective in endosomal transport to both the plasma membranes and lysosomes (Yoshimori et al., 2000). In the present study, we demonstrated that overexpression of SKD1(E235Q) using an adenovirus delivery system caused a defect in autophagy-dependent bulk protein degradation. Morphological observations suggested that this inhibition of autophagy results from an impairment of autolysosome formation. SKD1(E235Q) overexpression also inhibited transport from endosomes to autophagosomes, an event normally occurring prior to fusion with lysosomes. These results indicate that SKD1-dependent endosomal membrane trafficking is required for formation of autolysosomes.
authors.affiliation: Department of Cell Biology, National Institute for Basic Biology, Myodaiji, Okazaki, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: Nara
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kabeya
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D019943:Amino Acid Substitution; D001343:Autophagy / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000502:physiology*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008247:Lysosomes / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology; D010588:Phagosomes / Q000502:physiology; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases; D033921:Vesicular Transport Proteins
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D012097:Repressor Proteins; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human