Weak membrane interactions allow rheb to activate mTORC1 signaling without major lysosome enrichment.

08:00 EDT 18th September 2019 | BioPortfolio

Summary of "Weak membrane interactions allow rheb to activate mTORC1 signaling without major lysosome enrichment."

Stable localization of the Rheb GTPase to lysosomes is thought to be required for activation of mTORC1 signaling. However, the lysosome targeting mechanisms for Rheb remain unclear. We therefore investigated the relationship between Rheb subcellular localization and mTORC1 activation. Surprisingly, we found that Rheb was undetectable at lysosomes. Nonetheless, functional assays in knockout human cells revealed that farnesylation of the C-terminal CaaX motif on Rheb was essential for Rheb-dependent mTORC1 activation. Although farnesylated Rheb exhibited partial endoplasmic reticulum localization, constitutively targeting Rheb to ER membranes did not support mTORC1 activation. Further systematic analysis of Rheb lipidation revealed that weak, non-selective, membrane interactions support Rheb-dependent mTORC1 activation without the need for a specific lysosome targeting motif. Collectively, these results argue against stable interactions of Rheb with lysosomes and instead that transient membrane interactions optimally allow Rheb to activate mTORC1 signaling. [Media: see text].


Journal Details

This article was published in the following journal.

Name: Molecular biology of the cell
ISSN: 1939-4586
Pages: mbcE19030146


DeepDyve research library

PubMed Articles [14870 Associated PubMed Articles listed on BioPortfolio]

Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo.

We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of BDNF in the rat hippocampus in vivo. However, it is still unclear how neuronal BDNF pr...

Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway.

Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be ...

Differential regulation of mTORC1 activation by leucine and β-hydroxy-β-methylbutyrate in skeletal muscle of neonatal pigs.

Leucine and its metabolite β-hydroxy-β-methylbutyrate (HMB) stimulate mTORC1-dependent protein synthesis in the skeletal muscles of neonatal pigs. The aim of this study was to determine whether HMB ...

Cartilage ablation of Sirt1 causes inhibition of growth plate chondrogenesis by hyperactivation of mTORC1 signaling.

A growing body of evidence implied a pivotal role of Sirt1 in chondrocyte function and homeostasis, however, its underlying mechanisms mediating chondrogenesis which is an essential process for physio...

Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1.

Cancer cells rely on mTORC1 activity to coordinate mitogenic signaling with nutrients availability for growth. Based on the metabolic function of E2F1, we hypothesize that glucose catabolism driven by...

Clinical Trials [2471 Associated Clinical Trials listed on BioPortfolio]

Neoadjuvant Run-In Study With TAK-228 (MLN0128) Followed by Letrozole/TAK-228 (MLN0128) in Women With High-Risk ER+/HER2- Breast Cancer

Millennium has developed TAK-228, which is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to a...

ACTIVATE: A Computerized Training Program for Children With ADHD

A preliminary clinical trial of ACTIVATE will be conducted in a sample of children with ADHD. ACTIVATE is a computerized neurocognitive training program (ACTIVATE; see:

Metformin in Children and Adults With Fragile X Syndrome

Fragile X Syndrome (FXS) is caused by loss of FMR1 expression on the X chromosome that leads to increased mRNA translation, which results in hyperactivation of ERK (extracellular signal-re...

Effect of Whey Protein Hydrolysate on Human Muscle Protein Synthesis

Muscle protein synthesis can be stimulated by ingestion of protein sources, such as whey, casein or soy. Protein supplementation can be useful to restore protein turnover after exercise bu...

mTORC1 and Autophagy in Human Brown Adipocytes

The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose...

Medical and Biotech [MESH] Definitions

The interactions of particles responsible for their scattering and transformations (decays and reactions). Because of interactions, an isolated particle may decay into other particles. Two particles passing near each other may transform, perhaps into the same particles but with changed momenta (elastic scattering) or into other particles (inelastic scattering). Interactions fall into three groups: strong, electromagnetic, and weak. (From McGraw-Hill Encyclopedia of Science & Technology, 7th ed)

A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.

A multidomain protein that is highly conserved among multicellular organisms. It contains a ZZ-type ZINC FINGER domain, C-terminal UBIQUITIN - associated (UBA) domain, and interacts with many other signaling proteins and enzymes including, atypical PROTEIN KINASE C; TNF RECEPTOR-ASSOCIATED FACTOR 6; subunits of the mTORC1 complex, and CASPASE-8. It functions in AUTOPHAGY as a receptor for the degradation of ubiquitinated substrates, and to co-ordinate signaling in response to OXIDATIVE STRESS.

Signaling proteins that are ligands for the EPH FAMILY RECEPTORS. They are membrane-bound proteins that are attached to the CELL MEMBRANE either through a GLYCOINOSITOL PHOSPHOLIPID MEMBRANE ANCHOR or through a transmembrane domain. Many of the ephrins are considered important intercellular signaling molecules that control morphogenic changes during embryogenesis.

Type-I membrane glycoproteins that are expressed primarily on the surface of CD4 or CD8-positive T-CELLS; NATURAL KILLER CELLS; and some populations of B CELLS. They are characterized by an N-terminal, extracellular IMMUNOGLOBULIN-LIKE DOMAIN and a membrane-proximal IMMUNOGLOBULIN C2-SET DOMAIN. SLAMF receptors typically signal through homophilic interactions and are important for mediating the immune response and immune cell differentiation.

Quick Search

DeepDyve research library

Relevant Topic

Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...

Searches Linking to this Article