A New Link in the Chain from Amino Acids to mTORC1 Activation

Centre for Biological Sciences, Life Sciences Building (B85), University of Southampton, Southampton SO17 1BJ, UK.
Molecular cell (Impact Factor: 14.46). 10/2011; 44(1):7-8. DOI: 10.1016/j.molcel.2011.09.004
Source: PubMed

ABSTRACT A recent study reveals that the scaffold protein p62 plays a role in linking nutritional cues (amino acids) to the activation of mammalian target of rapamycin complex 1 (mTORC1), a protein kinase that controls cell size and proliferation.

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    ABSTRACT: Recent evidence suggests that an altered mammalian (mechanistic) target of rapamycin (mTOR) signaling pathway and its pharmacological modulation might be implicated in several neurological diseases including epileptogenesis. mTOR is a molecular sensor, which regulates protein synthesis, enhancing mRNA translation of genes involved in the regulation of cell proliferation and survival, working as part of two distinct multimeric complexes known as mTORC1 and mTORC2. mTOR is an evolutionarily highly conserved serine/threonine kinase belonging to the phosphoinositide 3-kinase-related kinase family and represents one of the most recently studied pathways in relation to epilepsy and epileptogenesis, due to its suggested pivotal role in many aspects of cellular proliferation and growth also including neurodegeneration, neurogenesis, and synaptic plasticity. In this review, we report the cellular and molecular features of mTOR and related pathways, analyze their function in the brain including all current related evidence of their role, and finally, discuss the possible involvement of mTOR signaling in epileptogenesis and epilepsy, giving further consideration to future developments in this area.
    Molecular Neurobiology 07/2012; DOI:10.1007/s12035-012-8314-5 · 5.29 Impact Factor
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    ABSTRACT: The target of rapamycin (TOR) is a central regulator controlling cell growth. TOR is highly conserved from yeast to mammals, and is deregulated in human cancers and diabetes. TOR complex 1 (TORC1) integrates signals from growth factors, cellular energy status, stress, and amino acids to control cell growth, mitochondrial metabolism, and lipid biosynthesis. The mechanisms of growth factors and cellular energy status in regulating TORC1 have been well established, whereas the mechanism by which amino acid induces TORC1 remains largely unknown. Recent studies revealed that Rag GTPases play a central role in the regulation of TORC1 activation in response to amino acids. In this review, we will discuss the recent progress in our understanding of Rag GTPase-regulated TORC1 activation in response to amino acids. Particular focus will be given to the function of Rag GTPases in TORC1 activation and how Rag GTPases are regulated by amino acids.
    Cellular and Molecular Life Sciences CMLS 12/2012; 70(16). DOI:10.1007/s00018-012-1195-y · 5.86 Impact Factor