Identification and expression of the first nonmammalian amyloid-ß precursor-like protein APLP2 in the amphibian Xenopus laevis

R.W.J. Collin, D. van Strien, J.A.M. Leunissen, G.J.M. Martens

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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 approximate to 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.
Original languageEnglish
Pages (from-to)1906-1912
JournalEuropean Journal of Biochemistry
Volume271
Issue number10
DOIs
Publication statusPublished - 2004

Fingerprint

Amyloid beta-Protein Precursor
Xenopus laevis
Amphibians
Amyloid
Xenopus
Mammals
Proteins
Conservation
Xenopus Proteins
Messenger RNA
Hoof and Claw
Protease Inhibitors
Anura
Vertebrates
Tail
Availability
Rodentia
Tissue
Alzheimer Disease
Amino Acids

Keywords

  • alzheimers-disease
  • messenger-rna
  • neurite outgrowth
  • binding
  • gene
  • app
  • brain
  • sequence
  • family
  • localization

Cite this

Collin, R.W.J. ; van Strien, D. ; Leunissen, J.A.M. ; Martens, G.J.M. / Identification and expression of the first nonmammalian amyloid-ß precursor-like protein APLP2 in the amphibian Xenopus laevis. In: European Journal of Biochemistry. 2004 ; Vol. 271, No. 10. pp. 1906-1912.
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title = "Identification and expression of the first nonmammalian amyloid-{\ss} 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 approximate to 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.",
keywords = "alzheimers-disease, messenger-rna, neurite outgrowth, binding, gene, app, brain, sequence, family, localization",
author = "R.W.J. Collin and {van Strien}, D. and J.A.M. Leunissen and G.J.M. Martens",
year = "2004",
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volume = "271",
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Identification and expression of the first nonmammalian amyloid-ß precursor-like protein APLP2 in the amphibian Xenopus laevis. / Collin, R.W.J.; van Strien, D.; Leunissen, J.A.M.; Martens, G.J.M.

In: European Journal of Biochemistry, Vol. 271, No. 10, 2004, p. 1906-1912.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Identification and expression of the first nonmammalian amyloid-ß precursor-like protein APLP2 in the amphibian Xenopus laevis

AU - Collin, R.W.J.

AU - van Strien, D.

AU - Leunissen, J.A.M.

AU - Martens, G.J.M.

PY - 2004

Y1 - 2004

N2 - 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 approximate to 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.

AB - 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 approximate to 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.

KW - alzheimers-disease

KW - messenger-rna

KW - neurite outgrowth

KW - binding

KW - gene

KW - app

KW - brain

KW - sequence

KW - family

KW - localization

U2 - 10.1111/j.1432-1033.2004.04100.x

DO - 10.1111/j.1432-1033.2004.04100.x

M3 - Article

VL - 271

SP - 1906

EP - 1912

JO - European Journal of Biochemistry

JF - European Journal of Biochemistry

SN - 0014-2956

IS - 10

ER -