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Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Delivery Pathways to the Lysosome01:36

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Related Experiment Video

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Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Rags connect mTOR and autophagy.

Masashi Narita1, Ken Inoki

  • 1Cancer Research; UK Cambridge Research Institute, Cambridge, UK. Masashi.Narita@cancer.org.uk

Small Gtpases
|July 14, 2012
PubMed
Summary

The mechanistic target of rapamycin (mTOR) pathway is activated by nutrients via lysosomes. A novel TOR-autophagy spatial coupling compartment (TASCC) links mTOR and autophagy, coordinating cell growth and breakdown.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin (mTOR) pathway regulates protein synthesis and cell growth.
  • Nutrient availability, particularly amino acids, is a key activator of mTOR signaling.
  • Lysosomes are increasingly recognized as central hubs in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of lysosomes in amino acid-mediated mTOR activation.
  • To characterize a novel cytoplasmic compartment linking mTOR and autophagy.
  • To elucidate the function of Rag GTPases in mTOR localization and activation.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Confocal microscopy to visualize subcellular localization of mTOR and lysosomes.

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Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

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Analyzing Starvation-Induced Autophagy in the Drosophila melanogaster Larval Fat Body
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Analyzing Starvation-Induced Autophagy in the Drosophila melanogaster Larval Fat Body

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Study of Protein-protein Interactions in Autophagy Research
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  • Genetic manipulation of Rag GTPases to assess their role in mTOR signaling.

    • Main Results:

    • mTOR physically associates with lysosomes, a process mediated by Rag GTPases and the Ragulator complex.
    • A novel compartment, the TOR-autophagy spatial coupling compartment (TASCC), forms in oncogenic Ras-induced senescent cells.
    • TASCC formation facilitates the coordinated activation of mTOR and autophagy, requiring active Rag proteins.

    Conclusions:

    • Lysosomes are critical platforms for amino acid-mediated mTOR activation.
    • The TASCC represents a novel mechanism for coupling anabolic (mTOR) and catabolic (autophagy) processes.
    • Rag GTPases are essential for both lysosomal recruitment of mTOR and TASCC formation, impacting protein synthesis.