title: Identification and expression of the first nonmammalian amyloid-beta precursor-like protein APLP2 in the amphibian Xenopus laevis.
abstract: The Alzheimer's disease-linked amyloid-beta precursor protein (APP) belongs to a superfamily of proteins, which also comprises the amyloid-beta 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 approximately 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 mammalian-amphibian 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 delineate functionally important domains, and its overall high degree of conservation suggests an important role for this APP superfamily member.
authors.affiliation: Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences (NCMLS), University of Nijmegen, The Netherlands.
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Denise
authors.initials: D
authors.lastname: van Strien
authors.forename: Jack A M
authors.initials: JA
authors.lastname: Leunissen
authors.forename: Gerard J M
authors.initials: GJ
authors.lastname: Martens
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015870:Gene Expression; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins