Wang Wendy, Perens Elliot A, Oikonomou Grigorios, Wallace Sean W, Lu Yun, Shaham Shai
Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Dev Biol. 2017 Oct 1;430(1):105-112. doi: 10.1016/j.ydbio.2017.08.009. Epub 2017 Aug 10.
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.
感觉器官神经胶质细胞围绕神经元感受末梢（NREs），形成一个对神经元活动很重要的特殊区域，这让人联想到中枢神经系统中神经胶质包裹的突触。我们之前表明，一种与Patched相关的蛋白质DAF-6，在秀丽隐杆线虫两性感觉器官的神经胶质细胞中是限制感觉区域大小所必需的。LIT-1，一种类Nemo激酶，以及SNX-1，一种逆转录酶复合物成分，拮抗DAF-6并促进区域扩张。为了进一步探索区域大小控制的潜在机制，我们寻找那些失活后能使daf-6突变体恢复正常区域大小的基因。我们发现，igdb-2（编码一种含有免疫球蛋白样和纤连蛋白III型结构域的单次跨膜蛋白）的突变能抑制daf-6突变体的缺陷。IGDB-2在神经胶质细胞中起作用，它定位于围绕NREs的神经胶质细胞膜上，并且与LIT-1和SNX-1一起调节区域形态发生。免疫沉淀后进行质谱分析表明，IGDB-2与LGC-34（一种预测的配体门控离子通道）结合，并且lgc-34突变抑制了igdb-2对daf-6的抑制作用。我们的研究结果揭示了一种新的膜蛋白复合物，并提出了感觉区域大小如何被控制的可能机制。
