Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons

Date
2009
Authors
Hruska, M.
Keefe J.
Wert, D.
Tekinay, A.B.
Hulce J.J.
Ibañez-Tallon I.
Nishi, R.
Advisor
Supervisor
Co-Advisor
Co-Supervisor
Instructor
Source Title
Journal of Neuroscience
Print ISSN
0270-6474
Electronic ISSN
Publisher
Volume
29
Issue
47
Pages
14847 - 14854
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Series
Abstract

Vertebrate α-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases > 100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling-induced cell death during development. Copyright © 2009 Society for Neuroscience.

Course
Other identifiers
Book Title
Keywords
alpha bungarotoxin, bungarotoxin receptor, complementary DNA, neurotoxin, prostate stem cell antigen, RNA, virus vector, animal tissue, apoptosis, article, chick embryo, ciliary ganglion, controlled study, embryo development, gene expression, immunohistochemistry, mouse, nerve cell necrosis, nervous system development, nonhuman, parasympathetic nerve cell, priority journal, prostate cancer, real time polymerase chain reaction, telencephalon, Amino Acid Sequence, Animals, Apoptosis, Avian Proteins, Base Sequence, Chickens, Ganglia, Parasympathetic, Gene Expression Regulation, Developmental, Membrane Glycoproteins, Mice, Molecular Sequence Data, Neoplasm Proteins, Neurons, Neuropeptides, Neurotoxins, Nicotinic Agonists, Nicotinic Antagonists, Receptors, Nicotinic, Sequence Homology, Nucleic Acid, Telencephalon
Citation
Published Version (Please cite this version)