المؤلفون: Nava Segev, Zhanna Lipatova

المصدر: Cellular logistics. 4(3)

مصطلحات موضوعية: Endosome, Endocytic cycle, RAB1, Cell Biology, GTPase, Golgi apparatus, Biology, Biochemistry, Cell biology, Article Addendum, symbols.namesake, medicine.anatomical_structure, Lysosome, symbols, medicine, Molecular Medicine, Rab, Secretory pathway

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::565f994a053d62693620c50428cf78a8Test
https://pubmed.ncbi.nlm.nih.gov/25610722Test

المؤلفون: Zhanna Lipatova, Jonathan W. Mulholland, Nava Segev, Ankur H. Shah, Jane J. Kim

المصدر: Molecular Biology of the Cell

مصطلحات موضوعية: Saccharomyces cerevisiae Proteins, Golgi Apparatus, GTPase, Saccharomyces cerevisiae, Biology, Endoplasmic Reticulum, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Lysosome, Gene Expression Regulation, Fungal, medicine, Autophagy, Molecular Biology, 030304 developmental biology, 0303 health sciences, Endoplasmic reticulum, Membrane Proteins, Cell Biology, Articles, Golgi apparatus, Cell biology, Transport protein, Protein Transport, medicine.anatomical_structure, rab GTP-Binding Proteins, Membrane Trafficking, Mutation, Proteolysis, symbols, Unfolded protein response, Rab, Lysosomes, 030217 neurology & neurosurgery

الوصف: Ypt1 GTPase, in the context of an autophagy-specific module, regulates ER-phagy. Because Ypt1 is a known regulator of ER-to-Golgi transport, this means that a single Ypt/Rab can regulate two alternative transport steps from one compartment, the ER, to two different destinations, the Golgi and the autophagy pathway.
Accumulation of misfolded proteins on intracellular membranes has been implicated in neurodegenerative diseases. One cellular pathway that clears such aggregates is endoplasmic reticulum autophagy (ER-phagy), a selective autophagy pathway that delivers excess ER to the lysosome for degradation. Not much is known about the regulation of ER-phagy. The conserved Ypt/Rab GTPases regulate all membrane trafficking events in eukaryotic cells. We recently showed that a Ypt module, consisting of Ypt1 and autophagy-specific upstream activator and downstream effector, regulates the onset of selective autophagy in yeast. Here we show that this module acts at the ER. Autophagy-specific mutations in its components cause accumulation of excess membrane proteins on aberrant ER structures and induction of ER stress. This accumulation is due to a block in transport of these membranes to the lysosome, where they are normally cleared. These findings establish a role for an autophagy-specific Ypt1 module in the regulation of ER-phagy. Moreover, because Ypt1 is a known key regulator of ER-to-Golgi transport, these findings establish a second role for Ypt1 at the ER. We therefore propose that individual Ypt/Rabs, in the context of distinct modules, can coordinate alternative trafficking steps from one cellular compartment to different destinations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1484d74c6534006210bb0a7ffbde1d9fTest
https://pubmed.ncbi.nlm.nih.gov/23924895Test