INOSITOL TRANSPORT IN SACCHAROMYCES-CEREVISIAE IS REGULATED BY TRANSCRIPTIONAL AND DEGRADATIVE ENDOCYTIC MECHANISMS DURING THE GROWTH-CYCLETHAT ARE DISTINCT FROM INOSITOL-INDUCED REGULATION

Regulation of inositol uptake activity in Saccharomyces cerevisiae dur ing the growth cycle was examined. Activity increased as the cell popu lation transited from lag phase to exponential growth, and continued t o increase until late exponential phase. The increase in activity was due to increased transcription of the ITR1 gene and synthesis of the I tr1 permease. When the culture reached stationary phase, uptake activi ty decreased and dropped to a minimum within 4 h. The decrease was due to repression of ITR1 transcription, independent of the negative regu lator Opi1p, and degradation of the existing permease. Degradation dep ended on delivery of the permease to the vacuole through the END3/END4 endocytic pathway. During exponential growth in inositol-containing m edium the permease is also rapidly degraded, whereas in inositol-free medium the permease is highly stable. Rapid degradation of the permeas e at stationary phase occurred in inositol-free medium, indicating tha t there are two distinct mechanisms that trigger endocytosis and degra dation in response to different physiological stimuli. In addition, th e level of the enzyme required for inositol biosynthesis, inositol-1-p hosphate synthase, encoded by INO1, is not reduced in stationary-phase cells, and this contrast in the regulation of inositol supply is disc ussed.