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自噬依赖性管状溶酶体网络同步肌肉重塑所需的降解活性。

An autophagy-dependent tubular lysosomal network synchronizes degradative activity required for muscle remodeling.

机构信息

Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, 4259-S2-11 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.

Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8578, Japan.

出版信息

J Cell Sci. 2020 Nov 9;133(21):jcs248336. doi: 10.1242/jcs.248336.

Abstract

Lysosomes are compartments for the degradation of both endocytic and autophagic cargoes. The shape of lysosomes changes with cellular degradative demands; however, there is limited knowledge about the mechanisms or significance that underlies distinct lysosomal morphologies. Here, we found an extensive tubular autolysosomal network in abdominal muscle remodeling during metamorphosis. The tubular network transiently appeared and exhibited the capacity to degrade autophagic cargoes. The tubular autolysosomal network was uniquely marked by the autophagic SNARE protein Syntaxin17 and its formation depended on both autophagic flux and degradative function, with the exception of the Atg12 and Atg8 ubiquitin-like conjugation systems. Among -deficient mutants, the efficiency of lysosomal tubulation correlated with the phenotypic severity in muscle remodeling. The lumen of the tubular network was continuous and homogeneous across a broad region of the remodeling muscle. Altogether, we revealed that the dynamic expansion of a tubular autolysosomal network synchronizes the abundant degradative activity required for developmentally regulated muscle remodeling.

摘要

溶酶体是内吞和自噬货物降解的场所。溶酶体的形状随细胞降解需求而变化;然而,对于不同溶酶体形态背后的机制或意义知之甚少。在这里,我们发现在变态过程中腹部肌肉重塑过程中有广泛的管状自噬溶酶体网络。管状网络短暂出现,并表现出降解自噬货物的能力。管状自噬溶酶体网络由独特的自噬 SNARE 蛋白 Syntaxin17 标记,其形成取决于自噬流和降解功能,除了 Atg12 和 Atg8 泛素样连接系统。在 - 缺陷突变体中,溶酶体管化的效率与肌肉重塑中的表型严重程度相关。管状网络的腔在重塑肌肉的广泛区域内是连续和均匀的。总的来说,我们揭示了管状自噬溶酶体网络的动态扩展使发育调节的肌肉重塑所需的丰富降解活性同步化。

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