Supplementary material from "Ceramide-transfer protein-mediated ceramide transfer is a structurally tunable flow-inducing mechanism with structural feed-forward loops"

Published on 2018-06-13T14:45:39Z (GMT) by
This paper considers two models of ceramide-transfer protein (CERT)-mediated ceramide transfer at the <i>trans</i>-Golgi network proposed in the literature, <i>short distance shuttle</i> and <i>neck swinging</i>, and seeks <i>structural</i> (parameter-free) features of the two models, which rely exclusively on the peculiar interaction network and not on specific parameter values. In particular, it is shown that both models can be seen as flow-inducing systems, where the flows between pairs of species are tuned by the concentrations of other species, and suitable external inputs can <i>structurally</i> regulate ceramide transfer. In the short distance shuttle model, the amount of transferred ceramide is <i>structurally</i> tuned by active protein kinase D (PKD), both directly and indirectly, in a coherent feed-forward loop motif. In the neck-swinging model, the amount of transferred ceramide is <i>structurally</i> tuned by active PI4KIII<i>β</i>, while active PKD has an ambivalent effect, due to the presence of an incoherent feed-forward loop motif that directly inhibits ceramide transfer and indirectly promotes it; the <i>structural</i> role of active PKD is to favour CERT mobility in the cytosol. It is also shown that the influences among key variables often have <i>structurally</i> determined steady-state signs, which can help falsify the models against experimental traces.

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Giordano, Giulia (2018): Supplementary material from "Ceramide-transfer protein-mediated ceramide transfer is a structurally tunable flow-inducing mechanism with structural feed-forward loops". The Royal Society. Collection.