  Understanding the mechanisms by which cells coordinate their size with their
ability to divide has long attracted the interest of biologists. The Target of
Rapamycin (TOR) pathway is becoming increasingly recognized as a master
regulator of cell size, however less is known how TOR activity might be coupled
with the cell cycle. Here, we establish that mTOR complex 1 (mTORC1) promotes
cytokinesis through activation of a Rho GTPase-Rho Kinase (ROCK) signaling
cascade. Hyperactivation of mTORC1 signaling by depletion of any of its
negative regulators: TSC1, TSC2, PTEN, or DEPTOR, induces polyploidy in a
rapamycin-sensitive manner. mTORC1 hyperactivation-mediated polyploidization
occurs by a prolonged, but ultimately failed attempt at abcission followed by
re-fusion. Similar to the effects of ROCK2 overexpression, these mTORC1-driven
aberrant cytokinesis events are accompanied by increased Rho-GTP loading,
extensive plasma membrane blebbing, and increased actin-myosin contractility,
all of which can be rescued by either mTORC1 or ROCK inhibition. These results
provide evidence for the existence of a novel mTORC1-Rho-ROCK pathway during
cytokinesis and suggest that mTORC1 might play a critical role in setting the
size at which a mammalian cell divides.
