TOR signaling, phosphoinositols and carbon source utilization in cell growth

Garrett H. Anderson and James G. Umen

Plant Biology Laboratory, The Salk Institute, La Jolla, CA, U.S.A.

TOR (target of rapamycin) kinase is a key growth regulator. It serves as a convergence point and integrator of pathways that sense energy, nutrients and stress. TOR activity correlates with growth, and known TOR substrates in yeast and metazoans [this clarifies the ambiguity of referring to 'known TOR substrates' and then shortly thereafter stating 'little is known about TOR in Chlamydomonas'] include growth-regulatory proteins. Most of what is known about TOR has come from studies of heterotrophic eukaryotes; very little is known about how TOR signaling has evolved to accommodate the photosynthetic plastid in green plants and algae. Chloroplasts provide an intracellular source of energy and reduced carbon, and their function must be coordinated with other metabolic pathways to drive growth. We have undertaken a genetic screen for mutants hypersensitive to the TOR inhibitor rapamycin to identify conserved and novel components of TOR signaling in Chlamydomonas. Two of these mutants have lesions in genes encoding proteins involved in phosphoinositol metabolism. Both mutants show wild-type or near wild-type growth in minimal media in the absence of the drug. Interestingly, these mutants differ dramatically in their responses to acetate: one shows severe hypersensitivity to rapamycin in minimal media, but partial alleviation upon addition of acetate. The second shows moderate hypersensitivity to rapamycin in minimal media but strong exacerbation upon acetate addition. These findings suggest that TOR signaling and phosphoinositols may interact to control growth in response to carbon source availability. We are investigating the relationships among our mutants, TOR signaling, and phosphoinositol metabolism in the regulation of carbon source utilization and growth.

e-mail address of presenting author: ganderson@salk.edu