Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Neuroscientist. 2021 Feb;27(1):47-57. doi: 10.1177/1073858420913844. Epub 2020 Apr 23.
Axon bifurcation - a specific form of branching of somatosensory axons characterized by the splitting of the growth cone - is mediated by a cGMP-dependent signaling cascade composed of the extracellular ligand CNP (C-type natriuretic peptide), the transmembrane receptor guanylyl cyclase Npr2 (natriuretic peptide receptor 2), and the kinase cGKI (cGMP-dependent protein kinase I). In the absence of any one of these components, the formation of T-shaped axonal branches is impaired in neurons from DRGs (dorsal root ganglia), CSGs (cranial sensory ganglia) and MTNs (mesencephalic trigeminal neurons) in the murine spinal cord or hindbrain. Instead, axons from DRGs or from CSGs extend only either in an ascending or descending direction, while axons from MTNs either elongate within the hindbrain or extend via the trigeminal ganglion to the masseter muscles. Collateral formation from non-bifurcating stem axons is not affected by impaired cGMP signaling. Activation of Npr2 requires both binding of the ligand CNP as well as phosphorylation of serine and threonine residues at the juxtamembrane regions of the receptor. The absence of bifurcation results in an altered shape of termination fields of sensory afferents in the spinal cord and resulted in impaired noxious heat sensation and nociception whereas motor coordination appeared normal.
轴突分叉 - 一种感觉轴突分支的特定形式，其特征在于生长锥的分裂 - 由 cGMP 依赖性信号级联介导，该级联由细胞外配体 CNP（C 型利钠肽）、跨膜受体鸟苷酸环化酶 Npr2（利钠肽受体 2）和激酶 cGKI（cGMP 依赖性蛋白激酶 I）组成。在这些成分中的任何一种缺失的情况下，鼠脊髓或后脑中的背根神经节（DRG）、颅神经节（CSG）和中脑三叉神经神经元（MTN）中的神经元的 T 形轴突分支的形成受损。相反，来自 DRG 或 CSG 的轴突仅沿上升或下降方向延伸，而来自 MTN 的轴突在脑桥内伸长或通过三叉神经节延伸至咬肌。非分叉主干轴突的侧支形成不受 cGMP 信号转导受损的影响。Npr2 的激活需要配体 CNP 的结合以及受体近膜区域丝氨酸和苏氨酸残基的磷酸化。分叉的缺失导致脊髓中感觉传入的终止场的形状改变，并导致有害热感觉和伤害感受受损，而运动协调似乎正常。
