title: Regulation of membrane protein degradation by starvation-response pathways.
abstract: The multivesicular body (MVB) pathway delivers membrane proteins to the lumen of the vacuole/lysosome for degradation. The resulting amino acids are transported to the cytoplasm for reuse in protein synthesis. Our study shows that this amino acid recycling system plays an essential role in the adaptation of cells to starvation conditions. Cells respond to amino acid starvation by upregulating both endocytosis and the MVB pathway, thereby providing amino acids through increased protein turnover. Our data suggest that increased Rsp5-dependent ubiquitination of membrane proteins and a drop in Ist1 levels, a negative regulator of endosomal sorting complex required for transport (ESCRT) activity, cause this response. Furthermore, we found that target of rapamycin complex 1 (TORC1) and a second, unknown nutrient-sensing system are responsible for the starvation-induced protein turnover. Together, the data indicate that protein synthesis and turnover are linked by a common regulatory system that ensures adaptation and survival under nutrient-stress conditions.
authors: Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112-9202, USA.
authors: Charles B
authors: CB
authors: Jones
authors: Elizabeth M
authors: EM
authors: Ott
authors: Justin M
authors: JM
authors: Keener
authors: Matt
authors: M
authors: Curtiss
authors: Virginie
authors: V
authors: Sandrin
authors: Markus
authors: M
authors: Babst
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002470:Cell Survival; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D057146:Multivesicular Bodies / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D015854:Up-Regulation
chemical_list: D000596:Amino Acids; D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008565:Membrane Proteins