title: Regulation of selective autophagy onset by a Ypt/Rab GTPase module.
abstract: The key regulators of intracellular trafficking, Ypt/Rab GTPases, are stimulated by specific upstream activators and, when activated, recruit specific downstream effectors to mediate membrane-transport events. The yeast Ypt1 and its human functional homolog hRab1 regulate both endoplasmic reticulum (ER)-to-Golgi transport and autophagy. However, it is not clear whether the mechanism by which these GTPases regulate autophagy depends on their well-documented function in ER-to-Golgi transport. Here, we identify Atg11, the preautophagosomal structure (PAS) organizer, as a downstream effector of Ypt1 and show that the Ypt1-Atg11 interaction is required for PAS assembly under normal growth conditions. Moreover, we show that Ypt1 and Atg11 colocalize with Trs85, a Ypt1 activator subunit, and together they regulate selective autophagy. Finally, we show that Ypt1 and Trs85 interact on Atg9-containing membranes, which serve as a source for the membrane component of the PAS. Together our results define a Ypt/Rab module--comprising an activator, GTPase, and effector--that orchestrates the onset of selective autophagy, a process vital for cell homeostasis. Furthermore, because Atg11 does not play a role in ER-to-Golgi transport, we demonstrate here that Ypt/Rabs can regulate two independent membrane-transport processes by recruiting process-specific effectors.
authors.affiliation: Departments of Biochemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Lipatova
authors.forename: Natalia
authors.initials: N
authors.lastname: Belogortseva
authors.forename: Xiu Qi
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Jane
authors.initials: J
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Taussig
authors.forename: Nava
authors.initials: N
authors.lastname: Segev
mesh_terms: D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D010588:Phagosomes / Q000502:physiology; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C502923:Atg11 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins