Ultrastructural analysis of the membrane origin for autophagy

组织蛋白酶D缺陷（CD-/-）小鼠（神经元蜡样脂褐质沉积症（NCL）的小鼠模型）脑中的神经元具有丰富的自噬体和颗粒状嗜锇沉积物（GROD），这些沉积物通常存在于新生的自噬体中。除了LC 3和泛素的免疫细胞化学定位外，还发现p62和Nbr 1也定位在GROD的膜上，这两种蛋白都可以与泛素和LC 3相互作用。此外，这些分子存在于神经元的相同颗粒中。这些数据表明，GRODs膜上的泛素和p62和/或Nbr 1可能作为自噬信号，有助于NCL的发病机制。

Neurons in brains of cathepsin D-deficient (CD-/-) mice, a murine model for neuronal ceroid lipofuscinoses (NCLs), possess abundant autophagosomes and granular osmiophilic deposits (GRODs),which are often found in nascent autophagosomes. In addition to immunocytochemical localization of LC3 and ubiquitin in, p62 and Nbr1, both of which can interact with both ubiquitin and LC3, were found to be also localized on the membrane of GRODs. Moreover, these molecules were present in the same granules of the neurons. The data indicate that ubiquitin and p62 and/or Nbr1 on the membrane of GRODs may serve as a signal of autophagy that contributes to the pathogenesis of NCLs.