Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast
Synthetic genetic array analyses identify powerful genetic interactions between a thermosensitive allele (sec14-1 ts)ofthe structural gene for the major yeast phosphatidylinositol transfer protein (SEC14) and a structural gene deletion allele (tlg2?) for the Tlg2 target membrane-soluble N-ethylmalei...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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American Society for Cell Biology
2008
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| Online Access: | http://hdl.handle.net/20.500.11937/11743 |
| _version_ | 1848747887597453312 |
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| author | Mousley, Carl Tyeryar, K. Ile, K. Schaaf, G. Brost, R. Boone, C. Guan, X. Wenk, M. Bankaitis, V. |
| author_facet | Mousley, Carl Tyeryar, K. Ile, K. Schaaf, G. Brost, R. Boone, C. Guan, X. Wenk, M. Bankaitis, V. |
| author_sort | Mousley, Carl |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Synthetic genetic array analyses identify powerful genetic interactions between a thermosensitive allele (sec14-1 ts)ofthe structural gene for the major yeast phosphatidylinositol transfer protein (SEC14) and a structural gene deletion allele (tlg2?) for the Tlg2 target membrane-soluble N-ethylmaleimide-sensitive factor attachment protein receptor. The data further demonstrate Sec14 is required for proper trans-Golgi network (TGN)/endosomal dynamics in yeast. Paradoxically, combinatorial depletion of Sec14 and Tlg2 activities elicits trafficking defects from the endoplasmic reticulum, and these defects are accompanied by compromise of the unfolded protein response (UPR). UPR failure occurs downstream of Hac1 mRNA splicing, and it is further accompanied by defects in TOR signaling. The data link TGN/endosomal dynamics with ceramide homeostasis, UPR activity, and TOR signaling in yeast, and they identify the Sit4 protein phosphatase as a primary conduit through which ceramides link to the UPR. We suggest combinatorial Sec14/Tlg2 dysfunction evokes inappropriate turnover of complex sphingolipids in endosomes. One result of this turnover is potentiation of ceramide-activated phosphatase-mediated down-regulation of the UPR. These results provide new insight into Sec14 function, and they emphasize the TGN/endosomal system as a central hub for homeostatic regulation in eukaryotes. © 2008 by The American Society for Cell Biology. |
| first_indexed | 2025-11-14T06:56:17Z |
| format | Journal Article |
| id | curtin-20.500.11937-11743 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:56:17Z |
| publishDate | 2008 |
| publisher | American Society for Cell Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-117432023-02-22T06:24:21Z Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast Mousley, Carl Tyeryar, K. Ile, K. Schaaf, G. Brost, R. Boone, C. Guan, X. Wenk, M. Bankaitis, V. Synthetic genetic array analyses identify powerful genetic interactions between a thermosensitive allele (sec14-1 ts)ofthe structural gene for the major yeast phosphatidylinositol transfer protein (SEC14) and a structural gene deletion allele (tlg2?) for the Tlg2 target membrane-soluble N-ethylmaleimide-sensitive factor attachment protein receptor. The data further demonstrate Sec14 is required for proper trans-Golgi network (TGN)/endosomal dynamics in yeast. Paradoxically, combinatorial depletion of Sec14 and Tlg2 activities elicits trafficking defects from the endoplasmic reticulum, and these defects are accompanied by compromise of the unfolded protein response (UPR). UPR failure occurs downstream of Hac1 mRNA splicing, and it is further accompanied by defects in TOR signaling. The data link TGN/endosomal dynamics with ceramide homeostasis, UPR activity, and TOR signaling in yeast, and they identify the Sit4 protein phosphatase as a primary conduit through which ceramides link to the UPR. We suggest combinatorial Sec14/Tlg2 dysfunction evokes inappropriate turnover of complex sphingolipids in endosomes. One result of this turnover is potentiation of ceramide-activated phosphatase-mediated down-regulation of the UPR. These results provide new insight into Sec14 function, and they emphasize the TGN/endosomal system as a central hub for homeostatic regulation in eukaryotes. © 2008 by The American Society for Cell Biology. 2008 Journal Article http://hdl.handle.net/20.500.11937/11743 10.1091/mbc.E08-04-0426 American Society for Cell Biology unknown |
| spellingShingle | Mousley, Carl Tyeryar, K. Ile, K. Schaaf, G. Brost, R. Boone, C. Guan, X. Wenk, M. Bankaitis, V. Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title | Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title_full | Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title_fullStr | Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title_full_unstemmed | Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title_short | Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast |
| title_sort | trans-golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and tor signaling in yeast |
| url | http://hdl.handle.net/20.500.11937/11743 |