Escandón E, Soppet D, Rosenthal A, Mendoza-Ramírez J L, Szönyi E, Burton L E, Henderson C E, Parada L F, Nikolics K
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080-4990.
J Neurosci. 1994 Apr;14(4):2054-68. doi: 10.1523/JNEUROSCI.14-04-02054.1994.
Members of the NGF family of proteins act as neurotrophic agents for defined populations of peripheral and central neurons during embryonic and postnatal development. We have studied the presence of receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4/5 (NT-3, NT-4/5) by cross-linking radioiodinated neurotrophins to specific cell surface receptors. We have identified neurotrophin receptors representing full-length TrkB and TrkC and their truncated forms (lacking a functional cytoplasmic kinase domain) in neuronal as well as in non-neuronal tissues. During chicken embryonic and early postnatal brain development, expression of full-length TrkB and TrkC proteins preceded the onset of the truncated forms of these receptors. A similar pattern was also observed in mouse embryonic and early postnatal brain. The relative levels of neurotrophin receptors in the basal forebrain and in the hippocampus did not change significantly with age in mice. High levels of receptors for the three neurotrophins were detected in the nigrostriatal system. Full-length TrkB and TrkC receptors were found in chicken and rat embryonic ventral spinal cord, as well as on purified motoneurons. Again, truncated TrkB appeared significantly later than the full-length form on spinal motoneurons. In chicken embryonic retina and optic tectum we detected full-length TrkB and TrkC; however, the optic tectum also expressed large amounts of the truncated form of TrkB. TrkC but not TrkB was detected in chicken embryonic skeletal muscle, suggesting that NT-3 may have a novel function in this tissue. The presence of neurotrophin receptors in a wide variety of embryonic and postnatal tissues underlines the significant role of BDNF, NT-3, and NT-4/5 in embryonic and postnatal development. The regulation of the ratio of full-length versus truncated neurotrophin receptors may play an important role in the development, maturation, and maintenance of various neuronal networks.
在胚胎期和出生后发育过程中，神经生长因子（NGF）家族的蛋白质成员作为特定外周和中枢神经元群体的神经营养因子发挥作用。我们通过将放射性碘化神经营养因子与特定细胞表面受体交联，研究了脑源性神经营养因子（BDNF）、神经营养素-3和-4/5（NT-3、NT-4/5）受体的存在情况。我们在神经元以及非神经元组织中鉴定出了代表全长TrkB和TrkC及其截短形式（缺乏功能性细胞质激酶结构域）的神经营养素受体。在鸡胚胎期和出生后早期的脑发育过程中，全长TrkB和TrkC蛋白的表达先于这些受体截短形式的出现。在小鼠胚胎期和出生后早期的脑中也观察到了类似的模式。小鼠基底前脑和海马体中神经营养素受体的相对水平随年龄变化不显著。在黑质纹状体系统中检测到了这三种神经营养素的高水平受体。在鸡和大鼠胚胎期腹侧脊髓以及纯化的运动神经元上发现了全长TrkB和TrkC受体。同样，截短的TrkB在脊髓运动神经元上出现的时间明显晚于全长形式。在鸡胚胎视网膜和视顶盖中我们检测到了全长TrkB和TrkC；然而，视顶盖也表达了大量截短形式的TrkB。在鸡胚胎骨骼肌中检测到了TrkC但未检测到TrkB，这表明NT-3可能在该组织中具有新功能。多种胚胎期和出生后组织中神经营养素受体的存在强调了BDNF、NT-3和NT-4/5在胚胎期和出生后发育中的重要作用。全长与截短神经营养素受体比例的调节可能在各种神经网络的发育、成熟和维持中发挥重要作用。
