Mammalian cells, including neurons, use macroautophagy (here ‘autophagy’) to degrade damaged proteins and organelles, and recycle nutrients in response to starvation and other forms of cell stress. The basic cellular machinery responsible for autophagy is highly conserved from yeast to mammals. However, evidence for specific adaptations to more complex organisms and in highly differentiated cells (e. g. neurons) remains limited. RILP (Rab interacting lysosomal protein) mediates retrograde transport of late endosomes (LEs) in nonneuronal mammalian cells. We have now found that RILP plays additional important, fundamental roles in neuronal autophagosome (AP) transport, and, more surprisingly, in AP biogenesis, and cargo turnover as well. RILP accomplishes these tasks via sequential interactions with key autophagosomal components — ATG5 and LC3 — as well as the microtubule motor protein cytoplasmic dynein (Figure 1A). We found further that RILP expression and behavior are controlled by MTOR kinase, linking RILP to a potentially wide range of physiological and pathophysiological functions.

包括神经元在内的哺乳动物细胞利用宏观自噬（此处称为“自噬”）降解受损的蛋白质和细胞器，并响应饥饿和其他形式的细胞应激而回收营养。从酵母到哺乳动物，高度保守负责自噬的基本细胞机制。但是，对于更复杂的生物体和高度分化的细胞（例如神经元）进行特殊适应的证据仍然有限。RILP（Rab相互作用溶酶体蛋白）介导非神经元哺乳动物细胞中晚期内体（LEs）的逆行运输。现在，我们发现RILP在神经元自噬体（AP）的运输中，以及在AP的生物发生和货物周转中也起着其他重要的基本作用。RILP通过与关键的自噬体组分ATG5和LC3以及微管运动蛋白胞质动力蛋白（图1A）的顺序相互作用来完成这些任务。我们进一步发现，RILP的表达和行为受MTOR激酶控制，从而将RILP与潜在的广泛生理和病理生理功能联系起来。