Studies of amino acid sensing by the mTORC 1 pathway

The mTOR complex 1 (mTORC 1) protein kinase is a master growth regulator that responds to multiple cues from the local and systemic environment surrounding the cell. Nutrients and growth factors are both required to activate mTORC 1 and to promote growth. While the mechanisms of growth factor signaling have been reasonably well established, we have only begun to unravel in recent years how amino acids signal to mTORC 1, thanks in large part to the identification of the Rag GTPases, which recruit mTORC 1 to the lysosomal surface for catalytic activation, and of the regulators of Rag function. An ultimate goal is to uncover the biochemical basis of the sensing event that triggers this signaling cascade in the first place: which amino acid(s) are sensed and how? Toward this end, we characterize in detail the amino acids required to fully activate mTORCl signaling in HEK-293T cells and identify SLC38A9 as a Rag-interacting amino acid transporter that may serve as an arginine sensor at the lysosome. Finally, we discuss the many open questions that remain to be studied regarding the mechanisms and logic behind amino acid sensing by the mTORC 1 pathway.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2016

Author dc:creator

• Wang, Shuyu, Ph. D. Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• David M. Sabatini.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/106737

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/106737