Open AccessA novel class of cysteine protease receptors that mediate lysosomal transport
Author(s) -
NakadaTsukui Kumiko,
Tsuboi Kumiko,
Furukawa Atsushi,
Yamada Yoko,
Nozaki Tomoyoshi
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01800.x
Subject(s) - biology , receptor , cysteine protease , endoplasmic reticulum , microbiology and biotechnology , entamoeba histolytica , secretion , transport protein , biochemistry , endocytic cycle , lysosome , endosome , protease , endocytosis , enzyme
Summary 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 .