Reinhardt R R, Chin E, Zhang B, Roth R A, Bondy C A
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland 20892.
J Neurosci. 1994 Aug;14(8):4674-83. doi: 10.1523/JNEUROSCI.14-08-04674.1994.
The insulin receptor-related receptor (IRR) has recently been identified as a member of the insulin receptor tyrosine kinase family; however, its endogenous ligand and biological function are still unknown. In contrast to the very widespread pattern of expression of the homologous insulin and IGF-I receptors, IRR demonstrates a very restricted cellular distribution. Using in situ hybridization and immunohistochemistry, we now show that the expression of this receptor is selectively concentrated in a subset of neurons where its appearance is closely associated with that of the NGF receptor TRK. IRR and TRK demonstrate synchronized patterns of coexpression in neural crest-derived sensory and sympathetic neurons and in non-neural crest basal forebrain and striatal neurons. Both appear early in the embryonic development of dorsal root and trigeminal neurons and somewhat later, near the time of birth, in sympathetic neurons. Expression of both IRR and TRK appears perinatally in basal forebrain neurons, reaching maximal levels about postnatal day 20. This association is highly selective, since TRK mRNA is not detected anywhere in the developing nervous system in the absence of coordinate IRR expression, and the same is true for IRR expression with respect to TRK. In the adult rat, the majority of TRK-positive sensory neurons still express IRR mRNA, and coexpression in sympathetic and forebrain neurons continues without evidence of diminution. These findings are consistent with a functional linkage of the IRR and TRK receptors in NGF-sensitive neurons.
胰岛素受体相关受体（IRR）最近被确定为胰岛素受体酪氨酸激酶家族的一员；然而，其内源配体和生物学功能仍不清楚。与同源的胰岛素和IGF-I受体广泛的表达模式不同，IRR表现出非常局限的细胞分布。利用原位杂交和免疫组织化学技术，我们现在表明该受体的表达选择性地集中在一部分神经元中，其出现与NGF受体TRK密切相关。IRR和TRK在神经嵴衍生的感觉和交感神经元以及非神经嵴基底前脑和纹状体神经元中表现出同步的共表达模式。两者都在背根和三叉神经元的胚胎发育早期出现，在交感神经元中出现稍晚，接近出生时。IRR和TRK在基底前脑神经元中围产期出现表达，在出生后第20天左右达到最高水平。这种关联具有高度选择性，因为在没有协调的IRR表达时，在发育中的神经系统中任何地方都检测不到TRK mRNA，对于IRR相对于TRK的表达也是如此。在成年大鼠中，大多数TRK阳性感觉神经元仍表达IRR mRNA，并且在交感和前脑神经元中的共表达持续存在且无减少迹象。这些发现与IRR和TRK受体在对NGF敏感的神经元中的功能联系一致。
