Journal Article


Heinrich J. Huber
Richard H. Middleton
Míriam R. García
Fernando Lopez-Caamal



cell proliferation initial conditions receptor activation cell death muscle cells muscle skeletal time and space hamilton institute

Positive Feedback in the AKT/mTOR pathway and its implications for growth signal progression in skeletal muscle cells: An analytical study (2012)

Abstract The IGF-1 mediated AKT/mTOR pathway has been recently proposed as mediator of skeletal muscle growth and a positive feedback between Akt and mTOR was suggested to induce homogenous growth signals along the whole spatial extension of such long cells. Here we develop two biologically justied approximations which we study under the presence of four dierent initial conditions that describe dierent paradigms of IGF-1 receptor{induced Akt/mTOR activation. In rst scenario the activation of the feedback cascade was assumed to be mild or protein turnover considered to be high. In turn, in the second scenario the transcriptional regulation was assumed to maintain dened levels of inactive pro{enzymes. For both scenarios, we were able to obtain closed{form formulas for growth signal progression in time and space and found that a localised initial signal maintains its Gaussian shape, but gets delocalised and exponentially degraded. Importantly, mathematical treatment of the reaction diusion system revealed that diusion ltered out high frequencies of spatially periodic initiator signals suggesting that the muscle cell is robust against uctuations in spatial receptor expression or activation. However, neither scenario was consistent with the presence of stably travelling signal waves. Our study highlights the role of feedback loops in spatiotemporal signal progression and results can be applied to studies in cell proliferation, cell dierentiation and cell death in other spatially extended cells.
Collections Ireland -> Maynooth University -> Type = Article
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering: Research Institutes: Hamilton Institute
Ireland -> Maynooth University -> Status = Published
Ireland -> Maynooth University -> Open Access DRIVERset

Full list of authors on original publication

Heinrich J. Huber, Richard H. Middleton, Míriam R. García, Fernando Lopez-Caamal

Experts in our system

Heinrich J Huber
Royal College of Surgeons in Ireland
Total Publications: 39
Richard H. Middleton
Maynooth University
Total Publications: 41