原创力文档tbc-2 is required for embryonic yolk protein storage and larval survival during l1 diapause in caenorhabditis eleganstbc-2需要存储和胚胎卵黄蛋白在l1滞育在线虫幼虫的生存.pdfVIP
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tbc-2 is required for embryonic yolk protein storage and larval survival during l1 diapause in caenorhabditis eleganstbc-2需要存储和胚胎卵黄蛋白在l1滞育在线虫幼虫的生存
TBC-2 Is Required for Embryonic Yolk Protein Storage
and Larval Survival during L1 Diapause in
Caenorhabditis elegans
¨ ´
Laetitia Chotard, Olga Skorobogata, Marc-Andre Sylvain, Sanhita Shrivastava, Christian E. Rocheleau*
Division of Endocrinology and Metabolism, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre Research Institute, McGill University,
Montreal, Quebec, Canada
Abstract
C. elegans first stage (L1) larvae hatched in the absence of food, arrest development and enter an L1 diapause, whereby they
can survive starvation for several weeks. The physiological and metabolic requirements for survival during L1 diapause are
poorly understood. However, yolk, a cholesterol binding/transport protein, has been suggested to serve as an energy
source. Here, we demonstrate that C. elegans TBC-2, a RAB-5 GTPase Activating Protein (GAP) involved in early-to-late
endosome transition, is important for yolk protein storage during embryogenesis and for L1 survival during starvation. We
found during embryogenesis, that a yolk::green fluorescent protein fusion (YP170::GFP), disappeared much more quickly in
tbc-2 mutant embryos as compared with wild-type control embryos. The premature disappearance of YP170::GFP in tbc-2
mutants is likely due to premature degradation in the lysosomes as we found that YP170::GFP showed increased
colocalization with Lysotracker Red, a marker for acidic compartments. Furthermore, YP170::GFP disappearance in tbc-2
mutants required RAB-7, a regulator of endosome to lysosome trafficking. Although tbc-2 is not essential in fed animals, we
discovered that tbc-2 mutant L1 larvae have strongly reduced survival when hatched in the absence of food. We show
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