molecular time-course and the metabolic basis of entry into dauer in caenorhabditis elegans分子时间进程和基础代谢进入多尔在秀丽隐杆线虫.pdfVIP

Molecular Time-Course and the Metabolic Basis of Entry into Dauer in Caenorhabditis elegans ¤ Pan-Young Jeong , Min-Seok Kwon, Hyoe-Jin Joo, Young-Ki Paik* Department of Biochemistry, College of Life Sciences and Biotechnology, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Seoul, Korea Abstract When Caenorhabditis elegans senses dauer pheromone (daumone), signaling inadequate growth conditions, it enters the dauer state, which is capable of long-term survival. However, the molecular pathway of dauer entry in C. elegans has remained elusive. To systematically monitor changes in gene expression in dauer paths, we used a DNA microarray containing 22,625 gene probes corresponding to 22,150 unique genes from C. elegans. We employed two different paths: direct exposure to daumone (Path 1) and normal growth media plus liquid culture (Path 2). Our data reveal that entry into dauer is accomplished through the multi-step process, which appears to be compartmentalized in time and according to metabolic flux. That is, a time-course of dauer entry in Path 1 shows that dauer larvae formation begins at post-embryonic stage S4 (48 h) and is complete at S6 (72 h). Our results also suggest the presence of a unique adaptive metabolic control mechanism that requires both stage-specific expression of specific genes and tight regulation of different modes of fuel metabolite utilization to sustain the energy balance in the context of prolonged survival under adverse growth conditions. It is apparent that worms entering dauer stage may rely heavily on carbohydrate-based energy reserves, whereas dauer larvae utilize fat or glyoxylate cycle-based energy sources. We created a comprehensive web-based dauer metabolic database for C. elegans (www.DauerDB.org) that makes it possible to search any gen