Alpha 7 nicotinic receptors attenuate neurite development through calcium activation of calpain at the growth cone

PloS One
Justin R King, Nadine Kabbani

Abstract

The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth. α7 nAChR mediated EB3 comet motility, spectrin breakdown, and neurite growth was also inhibited by the addition of the selective calpain blocker calpeptin and attenuated by the expression of an α7 subunit unable to bind Gαq and activate calcium store release. The findings indicate that α7 nAChRs regulate cytoskeletal dynamics through local calcium signals for calpain protease activity.

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Citations

Apr 27, 2020·Cellular and Molecular Neurobiology·Kamilla MussinaOlena Filchakova
Oct 5, 2018·Journal of Proteome Research·Matthew J MulcahyEdward Hawrot

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Methods Mentioned

BETA
transfection
Fluorescence Recovery After Photobleach
protein assay
fluorescence imaging
fluorescence recovery after photobleaching

Software Mentioned

Zen
GeneSYS
Vaa3D
ImageJ
Image J

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