Rossi J, Luukko K, Poteryaev D, Laurikainen A, Sun Y F, Laakso T, Eerikäinen S, Tuominen R, Lakso M, Rauvala H, Arumäe U, Pasternack M, Saarma M, Airaksinen M S
Program of Molecular Neurobiology, Institute of Biotechnology, University of Helsinki, Finland.
Neuron. 1999 Feb;22(2):243-52. doi: 10.1016/s0896-6273(00)81086-7.
Glial cell line-derived neurotrophic factor (GDNF) and a related protein, neurturin (NTN), require a GPI-linked coreceptor, either GFR alpha1 or GFR alpha2, for signaling via the transmembrane Ret tyrosine kinase. We show that mice lacking functional GFR alpha2 coreceptor (Gfra2-/-) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation appeared normal, the parasympathetic cholinergic innervation was almost absent in the lacrimal and salivary glands and severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN at low concentrations were lacking in Gfra2-/- trigeminal neurons in vitro, whereas responses to GDNF were similar between the genotypes. Thus, GFR alpha2 is a physiological NTN receptor, essential for the development of specific postganglionic parasympathetic neurons.
胶质细胞系源性神经营养因子（GDNF）和一种相关蛋白——神经营养素（NTN），需要通过糖基磷脂酰肌醇（GPI）连接的共受体（GFRα1或GFRα2），才能经由跨膜Ret酪氨酸激酶进行信号传导。我们发现，缺乏功能性GFRα2共受体的小鼠（Gfra2-/-）能够存活且可育，但眼睛干涩，断奶后生长不良，推测是由于营养不良所致。虽然交感神经支配看似正常，但泪腺和唾液腺中几乎不存在副交感胆碱能神经支配，在小肠中也严重减少。在体外，Gfra2-/-三叉神经元缺乏低浓度NTN的神经突生长和营养作用，而不同基因型对GDNF的反应相似。因此，GFRα2是一种生理性NTN受体，对特定节后副交感神经元的发育至关重要。
