title: Ypt/Rab GTPases regulate two intersections of the secretory and the endosomal/lysosomal pathways.
abstract: A prevailing question in the Ypt/Rab field is whether these conserved GTPases are specific to cellular compartments. The established role for Ypt1 and its human homolog Rab1 is in endoplasmic reticulum (ER)-to-Golgi transport. More recently these regulators were implicated also in autophagy. Two different TRAPP complexes, I and III, were identified as the guanine-nucleotide-exchange factors (GEFs) of Ypt1 in ER-to-Golgi transport and autophagy, respectively. Confusingly, Ypt1 and TRAPP III were also suggested to regulate endosome-to-Golgi transport, implying that they function at multiple cellular compartments, and bringing into question the nature of Ypt/Rab specificity. Recently, we showed that the role of TRAPP III and Ypt1 in autophagy occurs at the ER and that they do not regulate endosome-to-Golgi transport. Here, we discuss the significance of this conclusion to the idea that Ypt/Rabs are specific to cellular compartments. We postulate that Ypt1 regulates 2 alternative routes emanating from the ER toward the Golgi and the lysosome/vacuole. We further propose that the secretory and endocytic/lysosomal pathways intersect in 2 junctures, and 2 Ypts, Ypt1 and Ypt31, coordinate transport in the 2 intersections: Ypt1 links ER-to-Golgi and ER-to-autophagy transport, whereas Ypt31 links Golgi-to-plasma membrane (PM) transport with PM-to-Golgi recycling through endosomes.
authors.affiliation: Department of Biochemistry and Molecular Genetics; University of Illinois at Chicago ; Chicago, IL USA.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Lipatova
authors.affiliation: Department of Biochemistry and Molecular Genetics; University of Illinois at Chicago ; Chicago, IL USA.
authors.forename: Nava
authors.initials: N
authors.lastname: Segev
keywords: ER-phagy; GTPase; Rab; TRAPP; Ypt1; Ypt31; cellular recycling; endosome-to-Golgi transport; secretory pathway