Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016.
The Helen L. and Martin S. Kimmel Center for Biology and Medicine, New York University School of Medicine, New York, NY 10016.
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E438-E447. doi: 10.1073/pnas.1712302115. Epub 2017 Dec 27.
Sensory neurons often possess cilia with elaborate membrane structures that are adapted to the sensory modality of the host cell. Mechanisms that target sensory transduction proteins to these specialized membrane domains remain poorly understood. Here, we show that a homolog of the human retinal dystrophy gene () is a Golgi-associated protein required for efficient trafficking of a sensory receptor, the receptor-type guanylate cyclase GCY-9, to cilia in chemosensory neurons of the nematode The trafficking defect caused by mutation of the nematode homolog is suppressed in vivo by mutation of key components of the retromer complex, which mediates recycling of cargo from endosomes to the Golgi. Our data show that there exists a critical balance in sensory neurons between the rates of anterograde and retrograde trafficking of cargo destined for the sensory cilium and this balance requires molecular specialization at an early stage of the secretory pathway.
感觉神经元通常具有纤毛，纤毛具有精细的膜结构，这些结构适应于宿主细胞的感觉模式。将感觉转导蛋白靶向到这些特化的膜结构域的机制仍知之甚少。在这里，我们发现人类视网膜退行性疾病基因 () 的一个同源物是一种高尔基相关蛋白，对于将感觉受体——受体型鸟苷酸环化酶 GCY-9——有效地运输到线虫化学感觉神经元的纤毛中是必需的。线虫 同源物突变引起的运输缺陷可以通过逆转录复合物关键成分的突变在体内得到抑制，该复合物介导从内体到高尔基的货物的再循环。我们的数据表明，在感觉神经元中，定向感觉纤毛的货物的正向和逆行运输之间存在一个关键的平衡，这种平衡需要在分泌途径的早期阶段进行分子特化。
