Abcam dot blot protocol1/1/2024 Studies show that α7 nAChRs can signal through both ionotropic and metabotropic modes in neural and immune cells 7. The α7 nAChR is a widespread homopentameric channel receptor that activates calcium within cells 6. In addition to their post-synaptic localization, nAChRs are also found presynaptically and can contribute to synaptic growth and neurotransmitter release in brain circuits for memory and cognitive processing 5. Amongst the primary molecular components of the cholinergic synapse are ACh binding receptors such as the ligand-gated nicotinic acetylcholine receptor channel (nAChR) 4. The cholinergic synapse is among the most well understood synapses within many organisms, serving as a prototype for classical neurotransmission 2, 3. Taken together, our findings define mTOR as a novel pathway activated by T30 interaction with the nAChR and suggest a role for this process in human disease.Īcetylcholine (ACh) is an abundant neurotransmitter in the brain and periphery important for various physiological functions including movement, memory, and immune system regulation 1. These findings are corroborated in hippocampal neurons and show that T30 promotes dendritic arborization. T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E and S6K1, and a decrease in the autophagy LC3B-II protein. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and ⍺7 nAChR activation. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Proteomic analysis of cells exposed to (100 nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI–MS/MS). In particular, enzymatic cleavage of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the ⍺7 nicotinic acetylcholine receptor (nAChR) at synapses. AChE has also been shown to participate in non-enzymatic activity and contribute to cellular development and aging. Acetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery.
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