An RNautophagy/DNautophagy receptor, LAMP2C, possesses an arginine-rich motif that mediates RNA/DNA-binding
An RNautophagy/DNautophagy receptor, LAMP2C, possesses an arginine-rich motif that mediates RNA/DNA-binding
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DOI：
10.1016/j.bbrc.2015.03.025
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Kabuta, Tomohiro
中科院分区：
文献类型：
--
作者：
Fujiwara, Yuuki;Hase, Katsunori;Kabuta, Tomohiro
溶酶体是多种细胞成分降解的场所。我们最近发现了新的溶酶体系统，我们称之为RNautophagy和DNautophagy。在这些系统中，RNA和DNA分别被直接输入到溶酶体中并被降解。溶酶体膜蛋白LAMP 2C被鉴定为这些途径的受体。LAMP 2C的短C-末端胞质尾直接结合RNA和DNA。在这项研究中，我们研究了LAMP 2C的胞质序列识别核酸的机制。我们发现，该序列具有富含精氨酸基序的特征，这是一种在广泛的RNA结合蛋白中发现的RNA识别基序。LAMP 2C胞质序列中精氨酸残基的取代完全消除了其对核酸的结合能力。该序列的杂乱形式显示出与野生型序列相当的对RNA和DNA的亲和力，与其他富含精氨酸的基序的情况一样。我们还发现，其他LAMP家族蛋白，LAMP 1和CD 68/LAMP 4的胞质序列也具有精氨酸残基，并显示出对核酸的亲和力。我们的研究结果提供了进一步的深入了解RN自噬和DN自噬的机制，并可能有助于更好地了解溶酶体功能。(C)2015作者爱思唯尔公司出版这是CC BY许可下的开放获取文章。
Lysosomes are sites for the degradation of diverse cellular components. We recently discovered novel lysosomal systems we termed RNautophagy and DNautophagy. In these systems, RNA and DNA, respectively, are directly imported into lysosomes and degraded. A lysosomal membrane protein, LAMP2C was identified as a receptor for these pathways. The short C-terminal cytosolic tail of LAMP2C binds directly to both RNA and DNA. In this study, we examined the mechanisms underlying recognition of nucleic acids by the cytosolic sequence of LAMP2C. We found that the sequence possesses features of the arginine-rich motif, an RNA-recognition motif found in a wide range of RNA-binding proteins. Substitution of arginine residues in the LAMP2C cytosolic sequence completely abolished its binding capacity for nucleic acids. A scrambled form of the sequence showed affinity to RNA and DNA equivalent to that of the wild-type sequence, as is the case for other arginine-rich motifs. We also found that cytosolic sequences of other LAMP family proteins, LAMP1 and CD68/LAMP4, also possess arginine residues, and show affinity for nucleic acids. Our results provide further insight into the mechanisms underlying RNautophagy and DNautophagy, and may contribute to a better understanding of lysosome function. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.