FERM domain–containing protein 6 (FRMD6) is a member of the FERM protein superfamily, which is evolutionary highly conserved and has recently been identified as an upstream regulator of the conserved growth-promoting Hippo signaling pathway. In clinical studies, the FRMD6 gene is correlated with high significance to Alzheimer’s disease and cognitive impairment implicating a wider role of this protein in the nervous system. Scare data are available on the localization of endogenous FRMD6 in neural tissues. Using a FRMD6-directed antiserum, we detected specific immunoreactivity in varicose nerve fibers in the rat central and peripheral nervous system. FRMD6-immunoreactive (-ir) neurons were found in the sensory ganglia of cranial nerves, which were marked by a pool of labeled cytoplasmic granules. Cross-species comparative studies detected a morphologically identical fiber population and a comparable fiber distribution in tissues from xenopus and human cranial nerves and ganglia. In the spinal cord, FRMD6-ir was detectable in the terminal endings of primary afferent neurons containing substance P (SP). In the rat diencephalon, FRMD6-ir was co-localized with either SP- or arginine vasopressin–positive fibers in Broca’s diagonal band and the lateral septum. Dense fiber terminals containing both FRMD6-ir and growth hormone-releasing hormone were found in the median eminence. The intimate association of FRMD6 with secretory vesicles was investigated in vitro. Induction of exocytotic vesicles in cultured cells by ectopic expression of the SP precursor molecule preprotachykinin A led to a redistribution and co-localization of endogenous FRMD6 with secretory granules closely mimicking the observations in tissues.

中文翻译：

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含 FERM 结构域的蛋白 6 鉴定了不同脊椎动物物种中曲张神经纤维的亚群


含 FERM 结构域的蛋白 6 (FRMD6) 是 FERM 蛋白超家族的成员，该家族在进化上高度保守，最近被确定为保守的促生长 Hippo 信号通路的上游调节因子。在临床研究中，FRMD6 基因与阿尔茨海默病和认知障碍具有高度相关性，表明该蛋白质在神经系统中发挥着更广泛的作用。关于内源性 FRMD6 在神经组织中的定位有令人恐惧的数据。使用 FRMD6 定向抗血清，我们检测到大鼠中枢和周围神经系统中曲张神经纤维的特异性免疫反应性。在脑神经的感觉神经节中发现了 FRMD6 免疫反应性 (-ir) 神经元，这些神经节由一组标记的细胞质颗粒标记。跨物种比较研究发现爪蟾和人类脑神经和神经节的组织中形态相同的纤维群和类似的纤维分布。在脊髓中，在含有 P 物质 (SP) 的初级传入神经元末端可检测到 FRMD6-ir。在大鼠间脑中，FRMD6-ir 与布罗卡对角带和侧隔膜中的 SP- 或精氨酸加压素阳性纤维共定位。在正中隆起中发现了含有 FRMD6-ir 和生长激素释放激素的致密纤维末端。在体外研究了 FRMD6 与分泌囊泡的密切关联。通过 SP 前体分子前速激肽 A 的异位表达诱导培养细胞中的胞吐囊泡，导致内源性 FRMD6 与分泌颗粒的重新分布和共定位，这与组织中的观察结果非常相似。