Analysis of function and expression of the chick GPA receptor (GPAR alpha) suggests multiple roles in neuronal development
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Analysis of function and expression of the chick GPA receptor (GPAR alpha) suggests multiple roles in neuronal development. / Heller, S; Finn, T P; Huber, J; Nishi, R; Geissen, M; Püschel, A W; Rohrer, H.
in: DEVELOPMENT, Jahrgang 121, Nr. 8, 08.1995, S. 2681-2693.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Analysis of function and expression of the chick GPA receptor (GPAR alpha) suggests multiple roles in neuronal development
AU - Heller, S
AU - Finn, T P
AU - Huber, J
AU - Nishi, R
AU - Geissen, M
AU - Püschel, A W
AU - Rohrer, H
PY - 1995/8
Y1 - 1995/8
N2 - Growth promoting activity (GPA) is a chick growth factor with low homology to mammalian ciliary neurotrophic factor (CNTF) (47% sequence identity with rat CNTF) but displays similar biological effects on neuronal development. We have isolated a chick cDNA coding for GPA receptor (GPAR alpha), a GPI-anchored protein that is 70% identical to hCNTFR alpha. Functional analysis revealed that GPAR alpha mediates several biological effects of both GPA and CNTF. Soluble GPAR alpha supports GPA- and CNTF-dependent survival of human TF-1 cells. In sympathetic neurons, GPAR alpha mediates effects of both GPA and CNTF on the expression of vasoactive intestinal peptide (VIP) as shown by the inhibition of GPA- and CNTF-mediated VIP induction upon GPAR alpha antisense RNA expression. These results demonstrate that GPAR alpha is able to mediate effects of two neurokines that are only distantly related. GPAR alpha mRNA expression is largely restricted to the nervous system and was detected in all neurons that have been shown to respond to GPA or CNTF by increased survival or differentiation, i.e. ciliary, sympathetic, sensory dorsal root, motoneurons, retinal ganglion cells and amacrine cells. Interestingly, GPAR alpha mRNA was additionally found in neuronal populations and at developmental periods not known to be influenced by GPA or CNTF, suggesting novel functions for GPAR alpha and its ligands during neurogenesis and neuron differentiation.
AB - Growth promoting activity (GPA) is a chick growth factor with low homology to mammalian ciliary neurotrophic factor (CNTF) (47% sequence identity with rat CNTF) but displays similar biological effects on neuronal development. We have isolated a chick cDNA coding for GPA receptor (GPAR alpha), a GPI-anchored protein that is 70% identical to hCNTFR alpha. Functional analysis revealed that GPAR alpha mediates several biological effects of both GPA and CNTF. Soluble GPAR alpha supports GPA- and CNTF-dependent survival of human TF-1 cells. In sympathetic neurons, GPAR alpha mediates effects of both GPA and CNTF on the expression of vasoactive intestinal peptide (VIP) as shown by the inhibition of GPA- and CNTF-mediated VIP induction upon GPAR alpha antisense RNA expression. These results demonstrate that GPAR alpha is able to mediate effects of two neurokines that are only distantly related. GPAR alpha mRNA expression is largely restricted to the nervous system and was detected in all neurons that have been shown to respond to GPA or CNTF by increased survival or differentiation, i.e. ciliary, sympathetic, sensory dorsal root, motoneurons, retinal ganglion cells and amacrine cells. Interestingly, GPAR alpha mRNA was additionally found in neuronal populations and at developmental periods not known to be influenced by GPA or CNTF, suggesting novel functions for GPAR alpha and its ligands during neurogenesis and neuron differentiation.
KW - Amino Acid Sequence
KW - Animals
KW - Cell Differentiation/physiology
KW - Chick Embryo
KW - Ciliary Neurotrophic Factor
KW - DNA, Complementary/analysis
KW - Gene Expression
KW - Humans
KW - Molecular Sequence Data
KW - Nerve Growth Factors/genetics
KW - Nerve Tissue Proteins/genetics
KW - Nervous System/cytology
KW - Neurons/cytology
KW - Rats
KW - Receptors, Nerve Growth Factor/genetics
KW - Sequence Homology, Amino Acid
M3 - SCORING: Journal article
C2 - 7671828
VL - 121
SP - 2681
EP - 2693
JO - DEVELOPMENT
JF - DEVELOPMENT
SN - 0950-1991
IS - 8
ER -