Datensatz

Zusammenfassung

Cells that proliferate within a confined environment build up mechanical
compressive stress. For example, mechanical pressure emerges in the
naturally space-limited tumor environment. However, little is known
about how cells sense and respond to mechanical compression. We
developed microfluidic bioreactors to enable the investigation of the
effects of compressive stress on the growth of the genetically tractable
model organism Saccharomyces cerevisiae. We used this system to
determine that compressive stress is partly sensed through a module
consisting of the mucin Msb2 and the cell wall protein Sho1, which act
together as a sensor module in one of the two major osmosensing pathways
in budding yeast. This signal is transmitted via the MAPKKK kinase
Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway,
for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in
the G1 phase of the cell cycle and improves cell survival in response to
growth-induced pressure. We also found that the cell wall integrity
(CWI) pathway contributes to the response to mechanical compressive
stress. These latter results are confirmed in complimentary experiments
in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA,
10.1073/pnas. 1709079114]. When both the SMuSh and the CWI pathways are
deleted, cells fail to adapt to compressive stress, and all cells lyse
at relatively low pressure when grown in confinement. Thus, we define a
network that is essential for cell survival during growth under
pressure. We term this mechanosensory system the SCWISh (survival
through the CWI and SMuSh) network.