Date of Award

Spring 2013

First Advisor

Erin Johnson

Abstract

One of the central components in regulating cell growth and cell cycle progression is the mammalian target of Rapamycin (mTOR) complex. The mTOR complex consists of two distinct forms, mTORC1 and mTORC2. As aberrant mTOR complex activity is a major causative factor of many diseases including Polycystic Kidney Diseases (PKD), mTOR has become a major therapeutic target in the last decade. Rapamycin was the first macrolide drug known to inhibit mTOR activity, specifically inhibiting mTORC1. Recently, small-molecule-inhibitors such as Torin2 have been designed to directly bind the catalytic domain of mTOR in order to inhibit both mTORC1 and mTORC2. Using Rapamycin to block mTORC1, proximal tubular growth of Xenopus laevis can be partially abrogated. Here, we investigate whether Torin2 could further inhibit proximal tubular growth by blocking both mTORC1 and mTORC2 activity. Treatment with Torin2 showed greater proximal tubular growth inhibition than Rapamycin, which indicates both mTORC1 and mTORC2 are involved in proximal tubular development.

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