Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons.
The muscle-derived factors required for survival of embryonic motoneurons are not clearly identified. Cardiotrophin-1 (CT-1), a cytokine related to ciliary neurotrophic factor (CNTF), is expressed at high levels in embryonic limb bud and is secreted by differentiated myotubes. In vitro, CT-1 kept 43% of purified E14 rat motoneurons alive for 2 weeks (EC50 = 20 pM). In vivo, CT-1 protected neonatal sciatic motoneurons against the effects of axotomy. CT-1 action on motoneurons was inhibited by phosphatidylinositol-specific phospholipase C (PIPLC), suggesting that CT-1 may act through a GPI-linked component. Since no binding of CT-1 to CNTFR alpha was detected, CT-1 may use a novel cytokine receptor alpha subunit. CT-1 may be important in normal motoneuron development and as a potential tool for slowing motoneuron degeneration in human diseases.
Pennica
D
D
Department of Molecular Biology, Genentech Incorporated, South San Francisco, California 94080, USA.
Arce
V
V
Swanson
T A
TA
Vejsada
R
R
Pollock
R A
RA
Armanini
M
M
Dudley
K
K
Phillips
H S
HS
Rosenthal
A
A
Kato
A C
AC
Henderson
C E
CE
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D003714:Denervation; D004622:Embryo, Mammalian / Q000378:metabolism; D051379:Mice / Q000196:embryology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology*; D009132:Muscles / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000196:embryology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors
D016207:Cytokines; D015335:Molecular Probes; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C092073:cardiotrophin 1