University of Münster, Institute for Neuro- and Behavioral Biology, Badestrasse 9, 48149 Münster, Germany.
University of Münster, Institute for Neuro- and Behavioral Biology, Badestrasse 9, 48149 Münster, Germany
Development. 2020 Jan 22;147(2):dev181479. doi: 10.1242/dev.181479.
The development of tissues and organs requires close interaction of cells. To achieve this, cells express adhesion proteins such as the neural cell adhesion molecule (NCAM) or its ortholog Fasciclin 2 (Fas2). Both are members of the Ig-domain superfamily of proteins that mediate homophilic adhesion. These proteins are expressed as isoforms differing in their membrane anchorage and their cytoplasmic domains. To study the function of single isoforms, we have conducted a comprehensive genetic analysis of We reveal the expression pattern of all major Fas2 isoforms, two of which are GPI anchored. The remaining five isoforms carry transmembrane domains with variable cytoplasmic tails. We generated mutants expressing only single isoforms. In contrast to the null mutation, which causes embryonic lethality, these mutants are viable, indicating redundancy among the different isoforms. Cell type-specific rescue experiments showed that glial-secreted Fas2 can rescue the mutant phenotype to viability. This demonstrates that cytoplasmic Fas2 domains have no apparent essential functions and indicate that Fas2 has function(s) other than homophilic adhesion. In conclusion, our data suggest novel mechanistic aspects of a long-studied adhesion protein.
组织和器官的发育需要细胞的紧密相互作用。为了实现这一点，细胞表达粘附蛋白，如神经细胞粘附分子 (NCAM) 或其同源物 Fasciclin 2 (Fas2)。两者都是介导同种粘附的 Ig 结构域超家族蛋白的成员。这些蛋白作为膜锚定和细胞质结构域不同的同工型表达。为了研究单个同工型的功能，我们对所有主要 Fas2 同工型进行了全面的遗传分析，其中两种是 GPI 锚定的。其余五种同工型带有具有可变细胞质尾巴的跨膜结构域。我们生成了仅表达单个同工型的 突变体。与导致胚胎致死的缺失突变相反，这些突变体是存活的，表明不同同工型之间存在冗余。细胞类型特异性拯救实验表明，胶质细胞分泌的 Fas2 可以将 突变体的表型拯救到存活状态。这表明细胞质 Fas2 结构域没有明显的必需功能，并表明 Fas2 具有除同种粘附以外的功能。总之，我们的数据表明，这种长期研究的粘附蛋白具有新的机制方面。
