tailieunhanh - Báo cáo khoa học: Identification and expression of the first nonmammalian amyloid-b precursor-like protein APLP2 in the amphibian Xenopus laevis

The Alzheimer’s disease-linked amyloid-bprecursor pro-tein (APP) belongs to a superfamily of proteins, which also comprises the amyloid-b precursor-like proteins, APLP1 and APLP2. Whereas APP has been identified in both lower and higher vertebrates, thus far, APLP1 and 2 have been characterized only in human and rodents. Here we identify the first nonmammalian APLP2 protein in the South African claw-toed frogXenopus identity between the Xenopusand mammalian APLP2 proteins is 75%, with the highest degree of conservation in a number of amino-terminal regions, the transmembrane domain and the cytoplasmic tail | Eur. J. Biochem. 271 1906-1912 2004 FEBS 2004 doi Identification and expression of the first nonmammalian amyloid-b precursor-like protein APLP2 in the amphibian Xenopus laevis Rob W. J. Collin1 Denise van Strien1 Jack A. M. Leunissen2 and Gerard J. M. Martens1 1 Department of Molecular Animal Physiology Nijmegen Center for Molecular Life Sciences NCMLS University of Nijmegen the Netherlands 2Laboratory of Bioinformatics Wageningen University the Netherlands The Alzheimer s disease-linked amyloid-b precursor protein APP belongs to a superfamily of proteins which also comprises the amyloid-b precursor-like proteins APLP1 and APLP2. Whereas APP has been identified in both lower and higher vertebrates thus far APLP1 and 2 have been characterized only in human and rodents. Here we identify the first nonmammalian APLP2 protein in the South African claw-toed frog Xenopus laevis. The identity between the Xenopus and mammalian APLP2 proteins is w 75 with the highest degree of conservation in a number of amino-terminal regions the transmembrane domain and the cytoplasmic tail. Furthermore amino acid residues known to be phosphorylated and glycosylated in mammalian APLP2 are conserved in Xenopus. The availability of the Xenopus APLP2 protein sequence allowed a phylogenetic analysis of APP superfamily members that suggested the occurrence of APP and preAPLP lineages with their separation predating the mammalianamphibian split. As in mammals Xenopus APLP2 mRNA was ubiquitously expressed and alternatively spliced forms were detected. However the expression ratios between the mRNA forms in the various tissues examined were different between Xenopus and mammals most prominently for the alternatively spliced forms containing the Kunitz protease inhibitor-coding region that were less abundantly expressed than the corresponding mammalian forms. Thus the identification of APLP2 in Xenopus has revealed evolutionarily conserved regions that may help to