Preprint Article Version 1 This version is not peer-reviewed

Interplay between mTORC1 and mTORC2 in Regulating cAMP Signaling and Cell Adhesion in Dictyostelium discoideum

Version 1 : Received: 31 July 2024 / Approved: 31 July 2024 / Online: 31 July 2024 (09:55:26 CEST)

How to cite: Jaiswal, P. Interplay between mTORC1 and mTORC2 in Regulating cAMP Signaling and Cell Adhesion in Dictyostelium discoideum. Preprints 2024, 2024072536. https://doi.org/10.20944/preprints202407.2536.v1 Jaiswal, P. Interplay between mTORC1 and mTORC2 in Regulating cAMP Signaling and Cell Adhesion in Dictyostelium discoideum. Preprints 2024, 2024072536. https://doi.org/10.20944/preprints202407.2536.v1

Abstract

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

Keywords

 dictyostelium; cell adhesion; caffeine; mTORC1; mTORC2 

Subject

Biology and Life Sciences, Life Sciences

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