Calmodulin enhances mTORC1 signaling by preventing TSC2-Rheb binding.

ABSTRACT: The mechanistic target of rapamycin complex 1 (mTORC1) functions as a master regulator of cell growth and proliferation. We previously demonstrated that intracellular calcium ion (Ca²⁺) concentration modulates the mTORC1 pathway via binding of the Ca²⁺ sensor protein calmodulin (CaM) to tuberous sclerosis complex 2 (TSC2), a critical negative regulator of mTORC1. However, the precise molecular mechanism by which Ca²⁺/CaM modulates mTORC1 activity remains unclear. Here, we performed a binding assay based on nano-luciferase reconstitution, a method for detecting weak interactions between TSC2 and its target, Ras homolog enriched in the brain (Rheb), an activator of mTORC1. CaM inhibited the binding of TSC2 to Rheb in a Ca²⁺-dependent manner. Live-c

SUBMITTER: Amemiya Y 

PROVIDER: S-EPMC11787510 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature