title: An RNautophagy/DNautophagy receptor, LAMP2C, possesses an arginine-rich motif that mediates RNA/DNA-binding.
abstract: 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.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; Department of Electrical Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; Department of Electrical Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Hase
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. Electronic address: kabuta@ncnp.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D001343:Autophagy; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D012313:RNA / Q000378:metabolism*
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D012313:RNA; D004247:DNA; D001120:Arginine
keywords: Arginine-rich motif; DNautophagy; LAMP2C; Lysosome; RNautophagy