Direct uptake and degradation of DNA by lysosomes

被引:111
作者
Fujiwara, Yuuki [1 ,2 ]
Kikuchi, Hisae [1 ]
Aizawa, Shu [1 ]
Furuta, Akiko [1 ]
Hatanaka, Yusuke [1 ]
Konya, Chiho [1 ]
Uchida, Kenko [2 ]
Wada, Keiji [1 ]
Kabuta, Tomohiro [1 ]
机构
[1] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Kodaira, Tokyo 1870031, Japan
[2] Waseda Univ, Dept Elect Engn & Biosci, Grad Sch Adv Sci & Engn, Shinjuku Ku, Tokyo, Japan
基金
日本学术振兴会;
关键词
LAMP2; LAMP-2; LAMP2C; LAMP-2C; autophagy; RNA; RNautophagy; DNA; DNautophagy; CHAPERONE-MEDIATED AUTOPHAGY; MITOCHONDRIAL-DNA; RNA; PROTEINS; RECEPTOR; ISOFORMS;
D O I
10.4161/auto.24880
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Lysosomes contain various hydrolases that can degrade proteins, lipids, nucleic acids and carbohydrates. We recently discovered "RNautophagy," an autophagic pathway in which RNA is directly taken up by lysosomes and degraded. A lysosomal membrane protein, LAMP2C, a splice variant of LAMP2, binds to RNA and acts as a receptor for this pathway. In the present study, we show that DNA is also directly taken up by lysosomes and degraded. Like RNautophagy, this autophagic pathway, which we term "DNautophagy," is dependent on ATP. The cytosolic sequence of LAMP2C also directly interacts with DNA, and LAMP2C functions as a receptor for DNautophagy, in addition to RNautophagy. Similarly to RNA, DNA binds to the cytosolic sequences of fly and nematode LAMP orthologs. Together with the findings of our previous study, our present findings suggest that RNautophagy and DNautophagy are evolutionarily conserved systems in Metazoa.
引用
收藏
页码:1167 / 1171
页数:5
相关论文
共 27 条
[1]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[2]   TLR7: A new sensor of viral infection [J].
Crozat, K ;
Beutler, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (18) :6835-6836
[3]  
Cuervo AM, 2000, J CELL SCI, V113, P4441
[4]   A receptor for the selective uptake and degradation of proteins by lysosomes [J].
Cuervo, AM ;
Dice, JF .
SCIENCE, 1996, 273 (5274) :501-503
[5]   Chaperone-mediated autophagy [J].
Dice, J. Fred .
AUTOPHAGY, 2007, 3 (04) :295-299
[6]   Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA [J].
Diebold, SS ;
Kaisho, T ;
Hemmi, H ;
Akira, S ;
Sousa, CRE .
SCIENCE, 2004, 303 (5663) :1529-1531
[7]   TISSUE FRACTIONATION STUDIES .6. INTRACELLULAR DISTRIBUTION PATTERNS OF ENZYMES IN RAT-LIVER TISSUE [J].
DUVE, CD ;
PRESSMAN, BC ;
GIANETTO, R ;
WATTIAUX, R ;
APPELMANS, F .
BIOCHEMICAL JOURNAL, 1955, 60 (1-4) :604-617
[8]   Unifying nomenclature for the isoforms of the lysosomal membrane protein LAMP-2 [J].
Eskelinen, EL ;
Cuervo, AM ;
Taylor, MRG ;
Nishino, I ;
Blum, JS ;
Dice, JF ;
Sandoval, IV ;
Lippincott-Schwartz, J ;
August, JT ;
Saftig, P .
TRAFFIC, 2005, 6 (11) :1058-1061
[9]   Discovery of a novel type of autophagy targeting RNA [J].
Fujiwara, Yuuki ;
Furuta, Akiko ;
Kikuchi, Hisae ;
Aizawa, Shu ;
Hatanaka, Yusuke ;
Konya, Chiho ;
Uchida, Kenko ;
Yoshimura, Aya ;
Tamai, Yoshitaka ;
Wada, Keiji ;
Kabuta, Tomohiro .
AUTOPHAGY, 2013, 9 (03) :403-409
[10]   rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA [J].
Haud, Noemie ;
Kara, Firat ;
Diekmann, Simone ;
Henneke, Marco ;
Willer, Jason R. ;
Hillwig, Melissa S. ;
Gregg, Ronald G. ;
MacIntosh, Gustavo C. ;
Gaertner, Jutta ;
Alia, A. ;
Hurlstone, Adam F. L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (03) :1099-1103