title: A novel class of cysteine protease receptors that mediate lysosomal transport.
abstract: The transport of lysosomal proteins is, in general, mediated by mannose 6-phosphate receptors via carbohydrate modifications. Here, we describe a novel class of receptors that regulate the transport of lysosomal hydrolases in the enteric protozoan Entamoeba histolytica, which is a good model organism to investigate membrane traffic. A novel 110 kDa cysteine protease (CP) receptor (CP-binding protein family 1, CPBF1) was initially discovered by affinity co-precipitation of the major CP (EhCP-A5), which plays a pivotal role in the pathogenesis of E. histolytica. We demonstrated that CPBF1 regulates EhCP-A5 transport from the endoplasmic reticulum to lysosomes and its binding to EhCP-A5 is independent of carbohydrate modifications. Repression of CPBF1 by gene silencing led to the accumulation of the unprocessed form of EhCP-A5 in the non-acidic compartment and the mis-secretion of EhCP-A5, suggesting that CPBF1 is involved in the trafficking and processing of EhCP-A5. The CPBF represents a new class of transporters that bind to lysosomal hydrolases in a carbohydrate-independent fashion and regulate their trafficking, processing and activation and, thus, regulate the physiology and pathogenesis of E. histolytica.
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakada-Tsukui
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Furukawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Nozaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D057056:Cysteine Proteases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004748:Entamoeba histolytica / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006790:Host-Parasite Interactions; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D057056:Cysteine Proteases