<br>重新审视 LAMP1 作为神经系统中降解自噬溶酶体细胞器的标记。,Autophagy

当前位置： X-MOL 学术 › Autophagy › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

重新审视 LAMP1 作为神经系统中降解自噬溶酶体细胞器的标记。
Autophagy ( IF 14.6 ) Pub Date : 2018-06-27 , DOI: 10.1080/15548627.2018.1482147
Xiu-Tang Cheng ₁ , Yu-Xiang Xie ₁ , Bing Zhou ₁ , Ning Huang ₁ , Tamar Farfel-Becker ₁ , Zu-Hang Sheng ₁

Affiliation

溶酶体作为巨自噬/自噬和内吞成分的降解中心，从而维持神经元生存和功能所必需的细胞稳态。 LAMP1（溶酶体相关膜蛋白 1）和 LAMP2 分布在自噬细胞器和内溶酶体细胞器中。尽管分布广泛，但 LAMP1 通常用作溶酶体标记物，LAMP1 阳性细胞器通常称为溶酶体区室。通过应用免疫电子显微镜 (iTEM) 和共焦成像与 Airyscan 显微镜相结合，我们在有限的文献基础上进行了扩展，对神经元各种自噬和内溶酶体细胞器中 LAMP1 的分布进行了全面的定量分析。我们的研究表明，很大一部分 LAMP1 标记的细胞器缺乏主要的溶酶体水解酶。 BSA-金脉冲追踪测定进一步显示了 LAMP1 标记细胞器的异质降解能力。此外，LAMP1 强度并不是评估体内家族性肌萎缩侧索硬化症相关运动神经元溶酶体缺陷的敏感读数。因此，我们的研究在解释神经系统中 LAMP1 标记的细胞器时需要谨慎，其中 LAMP1 强度、运输和分布不一定代表生理和病理条件下的降解溶酶体或自溶酶体。缩写 ALS：肌萎缩侧索硬化症； BSA：牛血清白蛋白； DRG：背根神经节； IGF2R/CI-M6PR：胰岛素样生长因子2受体； iTEM：免疫透射电子显微镜； LAMP1/2：溶酶体相关膜蛋白1/2； P80：产后第80天； sMN：脊髓运动神经元。

"点击查看英文标题和摘要"

Revisiting LAMP1 as a marker for degradative autophagy-lysosomal organelles in the nervous system.

Lysosomes serve as the degradation hubs for macroautophagic/autophagic and endocytic components, thus maintaining cellular homeostasis essential for neuronal survival and function. LAMP1 (lysosomal associated membrane protein 1) and LAMP2 are distributed among autophagic and endolysosomal organelles. Despite widespread distribution, LAMP1 is routinely used as a lysosome marker and LAMP1-positive organelles are often referred to as lysosomal compartments. By applying immuno-electron microscopy (iTEM) and confocal imaging combined with Airyscan microscopy, we expand on the limited literature to provide a comprehensive and quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles lack major lysosomal hydrolases. BSA-gold pulse-chase assay further shows heterogeneous degradative capacities of LAMP1-labled organelles. In addition, LAMP1 intensity is not a sensitive readout to assess lysosomal deficits in familial amyotrophic lateral sclerosis-linked motor neurons in vivo. Our study thus calls for caution when interpreting LAMP1-labeled organelles in the nervous system where LAMP1 intensity, trafficking, and distribution do not necessarily represent degradative lysosomes or autolysosomes under physiological and pathological conditions. ABBREVIATIONS ALS: amyotrophic lateral sclerosis; BSA: bovine serum albumin; DRG: dorsal root ganglion; IGF2R/CI-M6PR: insulin like growth factor 2 receptor; iTEM: immuno-transmission electron microscopy; LAMP1/2: lysosomal associated membrane protein 1/2; P80: postnatal day 80; sMNs: spinal motor neurons.

更新日期：2018-07-23

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南