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Aging, Metabolism, Stress, Pathogenesis, and Small RNAs in C. elegans Topic Meeting 2012
Germline Stem Cells Regulate Somatic Proteostasis During
Caenorhabditis elegans Adulthood
Netta Shemesh, Nadav Shai, Anat Ben-Zvi
Ben-Gurion University of the Negev, Beer-Sheva, Israel
All cells rely on highly conserved protein folding and clearance pathways to detect
and resolve protein damage and maintain protein folding homeostasis (proteostasis). The
recognition that an age-associated imbalance in proteostasis is a potent contributor to the
onset of neurodegenerative diseases stresses the need to understand how protein folding is
regulated in a multi-cellular organism. We have noted that the ability of Caenorhabditis elegans
to maintain proteostasis declines sharply following the onset of oocyte biomass production,
suggesting that a restricted folding capacity may be linked to the onset of reproduction. To
test this hypothesis, we monitored the effects of different sterile mutations on proteostasis
maintenance in the soma of C. elegans. We find that germline stem cell (GSC) arrest rescued
protein quality control, resulting in maintenance of robust proteostasis in different somatic
tissues of adult animals. We further demonstrate that cell-nonautonomous signaling via kri-1,
a key player in GSC-dependent regulation of fat metabolism and longevity, is a mediator of
proteostasis maintenance in adulthood. We find that signaling through kri-1 and, specifically, the
activity of LIPL-4, a lipase that is regulated by KRI-1, can uncouple germline proliferation from
somatic proteostasis and prevent the switch between a robust and a limited state of proteostatic
capacity in the soma. This decreases the age-dependent accumulation of damaged proteins
and postpones the onset of age-dependent protein misfolding in a polyglutamine disease model.
Contact: anatbz@bgu.ac.il
Lab: Ben-Zvi
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Session 1