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EGF Receptor Transactivation is Crucial for Cholinergic MAP Kinase Signaling in Human Keratinocytes
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1  Institute of Biochemistry, Medical Faculty, Justus-Liebig-University Giessen


Acetylcholine and its receptors are not only essential for the nervous system but also act as mediators of cell communication between non-neuronal cells. Signal transduction after cholinergic stimulation is mediated by two types of receptors. The nicotinic acetylcholine receptors are ion channels, whereas the muscarinic receptors belong to the group of G protein coupled receptors (GPCR). Their activation can lead to initiation of the mitogen-activated protein (MAP) kinase cascade which contributes to cell survival, differentiation and other important cellular responses. The non-neuronal acetylcholine plays a substantial role in the human skin and regulates cell adhesion and migration, as well as proliferation and differentiation of keratinocytes. We here show that in the human keratinocyte cell line HaCaT, the muscarinic acetylcholine receptors are mediators of mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to an extensive activation of the MAP kinase ERK, together with an activation of the protein kinase Akt. These signaling pathways are dependent on the transactivation of the epidermal growth factor receptor (EGFR), and EGFR transactivation even appears to be the only pathway through which muscarinic receptors facilitate ERK activation in these cells. The transactivation pathway involves a triple-membrane-passing process, proceeding through the activation of matrix metalloproteases and an extracellular EGF-like ligand release.

Comments on this paper
Gian-Pietro Di Sansebastiano
endocytosis and acetylcholine
dear colleagues, your presentation attracted my attention because I know that EGF can alter multi-vesicular bodies formation and I am particularly interested to the topic and other related forms of "unconventional" traffic. Recently I spotted in plant cells an interesting effect of acetylcholine that was able (as auxin) to re-direct markers from an ER-to-Vacuole path to a Golgi-mediated one. I'd like to ask your opinion about the possibility that acetylcholine modify the organization of endocytic compartments but not endocytosis itself.
Did you, or will you, try other generic endocytic markers? As for example FM4-64?