signalling nutrient entry to cells

Zinzalla and Hall have writen an important review on how cells sense nutrients to control growth. The selection of nutrients between cells whether they be in the brain, muscle or elsewhere is a knowledge desert.
When we eat a meal how does the food get distributed before the eventual cell receives the nutrient.
There is also the distribution of carbohydrate, amino acids and lipids as well as the essential trace elements and vitamins.
It is possible to understand that when the cell requires trace elements or vitamins,the deficit is sent as a message to the cell surface and then the receptor signals needy to the blood and things happen.
How does the cell signal that amino acids or sugars or lipids are needed?
In mammalian cells, nutrients (such as amino acids), growth factors and cellular energy together trigger a molecular signalling pathway, mediated by the protein TOR, that controls cell growth. TOR inhibition by the anticancer drug rapamycin prevents unruly cell growth.
TOR (‘target of rapamycin’) is protein kinase found in two functionally and structurally distinct multiprotein complexes: TORC1 and TORC2. TORC1 controls many cellular processes that ultimately determine cell growth, including protein synthesis, ribosome formation, nutrient transport and autophagy (a survival mechanism that kicks in in response to starvation).
Activation of TORC1 requires simultaneous availability of amino acids, growth factors and energy. Inputs from growth factors (such as insulin) and energy contribute to the determination of that amino acids trigger TORC1 activation. Amino-acid depletion results in rapid dephosphorylation of two molecules downstream of TORC1, S6K and 4E-BP, whereas addition of amino acids leads to rapid, TORC1 -dependent phosphorylation of these molecules. But what is the molecular link between the amino-acid signal and TORCl activation?
Rag GTPases, heterodimers of RagA or RagB and RagC or RagD are involved in TORCl activation in response to this nutrient signal. By binding to TORCl, Rag GTPases mediate its transfer to intracellular membranes that contain another GTPase, Rheb. There, other signals such as cellular energy and growth factors (insulin) integrate with the amino-acid signal, leading to Rheb-mediated activation of TORCl and phosphorylation of its downstream effectors S6K and 4E-BP, which ultimately lead to protein synthesis and cell growth.
An very interesting start to understanding a key elements of nutrition.
Zinzalla and Hall 2008, Linking nutrients to growth. Nature vol 454 pp 287-8

Martin Eastwood
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