Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.
Vertebrate alpha-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 alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks alpha7-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 alpha7 signaling-induced cell death during development.
Hruska
Martin
M
Department of Anatomy, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Keefe
Julie
J
Wert
David
D
Tekinay
Ayse Begum
AB
Hulce
Jonathan J
JJ
Ibañez-Tallon
Ines
I
Nishi
Rae
R
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000235:genetics*; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D002645:Chickens; D058851:GPI-Linked Proteins; D005726:Ganglia, Parasympathetic / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D030161:Avian Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D009498:Neurotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C120222:Lynx1 protein, mouse; C510894:Lypd1 protein, mouse; C504399:Psca protein, mouse