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
2009Source Title
Journal of Neuroscience
Print ISSN
0270-6474
Volume
29
Issue
47
Pages
14847 - 14854
Language
English
Type
ArticleItem Usage Stats
113
views
views
80
downloads
downloads
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.
Keywords
alpha bungarotoxinbungarotoxin 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