AI Article Synopsis
- Eukaryotic cells feature two key protein kinase complexes, TORC1 and TORC2, which include TOR proteins as catalytic subunits and play crucial roles in sensing nutrients and stress while regulating cell growth.
- TORC1 is found on the vacuole or lysosome surface and promotes biosynthesis while inhibiting autophagy, while TORC2 is mainly located at the plasma membrane, helping to maintain membrane composition and support cell growth and division.
- The review discusses our current knowledge of TORC2's assembly, structure, location, and its functions and regulatory mechanisms, primarily based on recent studies.
Article Abstract
Every eukaryotic cell contains two distinct multisubunit protein kinase complexes that each contain a TOR (target of rapamycin) protein as the catalytic subunit. These ensembles, designated TORC1 and TORC2, serve as nutrient and stress sensors, signal integrators, and regulators of cell growth and homeostasis, but they differ in their composition, localization, and function. TORC1, activated on the cytosolic surface of the vacuole (or, in mammalian cells, on the cytosolic surface of the lysosome), promotes biosynthesis and suppresses autophagy. TORC2, located primarily at the plasma membrane (PM), maintains the proper levels and bilayer distribution of all PM components (sphingolipids, glycerophospholipids, sterols, and integral membrane proteins), which are needed for the membrane expansion that accompanies cell growth and division and for combating insults to PM integrity. This review summarizes our current understanding of the assembly, structural features, subcellular distribution, and function and regulation of TORC2, obtained largely through studies conducted with .
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1146/annurev-cellbio-011723-030346 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines.
Cells
December 2024
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla (US), 41012 Sevilla, Spain.
Autophagy is a catabolic process involved in different cellular functions. However, the molecular pathways governing its potential roles in different cell types remain poorly understood. We investigated the role of autophagy in the context of proteotoxic stress in two central nervous system cell types: the microglia-like cell line BV2 and the neuronal-like cell line N2a.
View Article and Find Full Text PDFCasein kinase 1 controls components of a TORC2 signaling network in budding yeast.
J Cell Sci
December 2024
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Article Synopsis
- TOR kinases are crucial for nutrient signaling and cell growth, organized into TORC1 and TORC2 complexes.
- In budding yeast, TORC2 is particularly important for regulating growth rate and cell size, but how it functions is not fully understood.
- Researchers discovered that the kinases Yck1 and Yck2 significantly impact the phosphorylation and localization of Mss4, a key player in TORC2 signaling, but their inhibition has minor effects on well-characterized pathways, indicating a potential role in less defined TORC2 functions.
Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.
ACS Pharmacol Transl Sci
December 2024
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurgaon-122413, Haryana, India.
The mechanistic target of rapamycin kinase (MTOR) is pivotal for cell growth, metabolism, and survival. It functions through two distinct complexes, mechanistic TORC1 and mechanistic TORC2 (mTORC1 and mTORC2). These complexes function in the development and progression of cancer by regulating different cellular processes, such as protein synthesis, lipid metabolism, and glucose homeostasis.
View Article and Find Full Text PDFNovel mTORC2/HSPB4 Interaction: Role and Regulation of HSPB4 T148 Phosphorylation.
Cells
December 2024
Department of Ophthalmology & Visual Sciences, The University of Michigan, Ann Arbor, MI 48109, USA.
HSPB4 and HSPB5 (α-crystallins) have shown increasing promise as neuroprotective agents, demonstrating several anti-apoptotic and protective roles in disorders such as multiple sclerosis and diabetic retinopathy. HSPs are highly regulated by post-translational modification, including deamidation, glycosylation, and phosphorylation. Among them, T148 phosphorylation has been shown to regulate the structural and functional characteristics of HSPB4 and underlie, in part, its neuroprotective capacity.
View Article and Find Full Text PDFTargeting mechanistic target of rapamycin complex 2 attenuates immunopathology in Systemic Lupus Erythematosus.
Rheumatology (Oxford)
December 2024
Division of Rheumatology, Department of Medicine, Mayo Clinic Rochester, MN, USA.
Objective: We aim to explore the role of mechanistic target of rapamycin complex (mTORC) 2 in systemic lupus erythematosus (SLE) development, the in vivo regulation of mTORC2 by type I interferon (IFN) signaling in autoimmunity, and to use mTORC2 targeting therapy to ameliorate lupus-like symptoms in an in vivo lupus mouse model and an in vitro coculture model using human PBMCs.
Method: We first induced lupus-like disease in T cell specific Rictor, a key component of mTORC2, deficient mice by topical application of imiquimod (IMQ) and monitored disease development. Next, we investigated the changes of mTORC2 signaling and immunological phenotypes in type I IFNAR deficient Lpr mice.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!