Signal transduction in human cells by metabolites derived from methionine and glucose

Organisms sense nutrients to match physiological responses to their environment. The mechanistic Target of Rapamycin complex I (mTORC1) pathway integrates information from a wide range of nutrient inputs to appropriately control cell growth. Nutrients like amino acids and glucose are required for mTORC1 to localize to the lysosome, its site of activation. The Rag-GTPases dictate mTORC1 localization and are regulated by GATOR1 and GATOR2 in response to nutrients, but how the GATOR-Rag axis senses nutrients is not completely understood. We found a novel protein, which we named SAMTOR, that interacts with GATOR1, and promotes GATOR1 activity and mTORC1 inhibition. Moreover, we show that SAMTOR is an S-adenosylmethionine binding protein, and that SAM binding disrupts the SAMTOR-GATOR1 interaction. SAM is a derivative of methionine, and we show that methionine starvation promotes SAMTOR action on GATOR1 following a decrease in SAM levels.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2021

Author dc:creator

• Orozco, Jose M.(Jose Miguel Orozco Segrera)

Advisor dc:contributor.advisor

• David M. Sabatini.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/131009

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/131009