The alpha component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development.
We recently proposed that ciliary neurotrophic factor (CNTF) shares two receptor components with a generally acting cytokine, leukemia inhibitory factor (LIF), but that CNTF also requires a third receptor component (CNTFR alpha) that is mostly restricted to the nervous system in its expression. Here we demonstrate that a transfected CNTFR alpha gene is sufficient to confer CNTF responsiveness upon hemopoietic cells normally responsive only to LIF, providing evidence that CNTFR alpha is a required receptor component that uniquely characterizes CNTF-responding cells. Consistent with this notion, CNTFR alpha expression could be localized to neurons within all known peripheral targets of CNTF. CNTFR alpha was also widely expressed within neurons of the CNS, suggesting that CNTF has broader CNS actions than previously appreciated. However, in vivo localization of CNTFR alpha, as well as of CNTF itself, is consistent with a particularly important role for CNTF in motor function as well as during neuropoiesis.
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Nancy Y
NY
Ip
Joyce
J
McClain
Nestor X
NX
Barrezueta
Thomas H
TH
Aldrich
Li
L
Pan
Yanping
Y
Li
Stanley J
SJ
Wiegand
Beth
B
Friedman
Samuel
S
Davis
George D
GD
Yancopoulos
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology / Q000378:metabolism; D001923:Brain Chemistry; D003001:Cloning, Molecular; D005724:Ganglia / Q000737:chemistry; D015870:Gene Expression; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology / Q000294:innervation / Q000378:metabolism; D009420:Nervous System / Q000196:embryology / Q000254:growth & development*; D009424:Nervous System Physiological Phenomena; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000196:embryology / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface