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IGDB-2 an Ig/FNIII protein binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans

机译:IGDB-2是一种Ig / FNIII蛋白与离子通道LGC-34结合并控制秀丽隐杆线虫的感觉区室形态发生

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摘要

Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants. We found that mutations in igdb-2, encoding a single-pass transmembrane protein containing Ig-like and fibronectin type III domains, suppress daf-6 mutant defects. IGDB-2 acts in glia, where it localizes to glial membranes surrounding NREs, and, together with LIT-1 and SNX-1, regulates compartment morphogenesis. Immunoprecipitation followed by mass spectrometry demonstrates that IGDB-2 binds to LGC-34, a predicted ligand-gated ion channel, and lgc-34 mutations inhibit igdb-2 suppression of daf-6. Our findings reveal a novel membrane protein complex and suggest possible mechanisms for how sensory compartment size is controlled.
机译:感觉器官的神经胶质细胞围绕神经元感受态末梢(NRE),形成一个对神经元活动很重要的专门区域,让人联想到神经胶质细胞在神经系统中的突触。我们先前显示,线虫两栖类感觉器官的神经胶质中需要DAF-6(与补丁相关的蛋白质),以限制感觉区室的大小。 LIT-1(一种Nemo样激酶)和SNX-1(一种逆转录剂组分)拮抗DAF-6并促进区室扩增。为了进一步探索潜在的区室大小控制机制,我们寻找了失活使daf-6突变体恢复正常区室大小的基因。我们发现,igdb-2中的突变编码包含Ig样和纤连蛋白III型结构域的单程跨膜蛋白,可以抑制daf-6突变体缺陷。 IGDB-2在胶质细胞中起作用,它定位于NRE周围的神经胶质膜,并与LIT-1和SNX-1一起调节隔室的形态发生。免疫沉淀和质谱分析表明,IGDB-2结合了LGC-34(一个预期的配体门控离子通道),lgc-34突变抑制了igdb-2对daf-6的抑制。我们的发现揭示了一种新型的膜蛋白复合物,并提出了如何控制感觉区室大小的可能机制。

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