Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells

Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.视紫红质（Rhodopsins, Rhs）是光感应蛋白，其中Rh1是果蝇光感受器视小杆膜中的主要视紫红质亚型。经光激活后，部分Rh1会发生内吞并降解，但目前尚不明确视小杆内的Rh1储备池如何得到补充，以及该过程涉及哪些分子调控因子。本研究证实，Crag作为一类DENN结构域蛋白，是Rab11的鸟苷酸交换因子，其对于光照条件下Rh1的稳态维持具有必需作用。Crag缺失会引发光照诱导的细胞质Rh1异常积累，而敲除Crag或Rab11均会导致成年果蝇出现相似的光感受器变性表型。进一步实验表明，Crag缺失引发的缺陷可通过组成型激活形式的Rab11得到部分挽救。我们据此提出：在光照刺激下，Crag依赖Rab11的囊泡运输途径，介导视紫红质从反式高尔基体网络转运至视小杆膜。