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Direct evidence for an adhesive function in the noncholinergic role of acetylcholinesterase in neurite outgrowth
Author(s) -
Sharma Karun V.,
Koenigsberger Carol,
Brimijoin Stephen,
Bigbee John W.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20010115)63:2<165::aid-jnr1008>3.0.co;2-o
Subject(s) - neurite , acetylcholinesterase , cell adhesion , microbiology and biotechnology , adhesion , aché , acetylcholine , chemistry , cell culture , cell adhesion molecule , cholinergic , cell , in vitro , biology , biochemistry , enzyme , neuroscience , endocrinology , genetics , organic chemistry
Acetylcholinesterase (AChE) can promote neurite outgrowth through a mechanism that is independent of its role in hydrolyzing the neurotransmitter acetylcholine. It has been proposed that this neuritogenic capacity of AChE may result from its intrinsic capacity to function in adhesion. In this study we directly tested this hypothesis using neuroblastoma cell lines that have been engineered for altered cell‐surface expression of AChE. Using a microtiter‐plate adhesion assay and the electrical cell‐substrate impedance‐sensing (ECIS) method, we demonstrate that the level of cell‐substratum adhesion of these cells directly correlates with their level of AChE expression. Furthermore, this adhesion is blocked by either an anti‐AChE antibody or a highly specific AChE inhibitor (BW284c51), both of which have also been shown to block neurite outgrowth. In addition, cells that overexpress AChE showed enhanced neurite initiation. By employing cell lines with different levels of AChE expression in two types of cell‐substratum adhesion assays, our current studies provide evidence for an adhesive function for AChE. These results, together with the fact that AChE shares sequence homology and structural similarities with several known cell adhesion molecules, support the hypothesis that AChE promotes neurite outgrowth, at least in part, through an adhesive function. J. Neurosci. Res. 63:165–175, 2001. © 2001 Wiley‐Liss, Inc.