Analysis of nicastrin gene phylogeny and expression in zebrafish.
NICASTRIN is a component of the aspartyl protease γ-secretase complex which is involved in intramembranous cleavage of type I transmembrane proteins, notably the Notch receptor proteins and the AMYLOID BETA A4 PRECURSOR PROTEIN (APP). This study aimed to characterize the orthologue of the human NICASTRIN (NCSTN) gene in zebrafish, an advantageous model organism for the study of human disease. Zebrafish Nicastrin protein was predicted to possess the conserved glutamate 333 residue and DYIGS motif of human NCSTN that are important for substrate recognition/processing in γ-secretase. Quantitative real-time RT-PCR revealed the profile of relative zebrafish nicastrin (ncstn) transcript levels in embryos at different times during development and in adult tissues. The analysis of synteny conservation revealed local rearrangements of ncstn and another gene, mpz, relative to copa, and pex19. In situ hybridization showed higher relative levels of ncstn transcripts in the developing brain and otic vesicles of embryos at 24 and 48 h post fertilization, respectively. Our observations are consistent with a role for Ncstn protein in Notch signaling within the proliferative ventricular zone of the developing central nervous system.
Alzheimer's disease Genetics Laboratory, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia, anne.lim@adelaide.edu.au.
Anne
A
Lim
Seyyed Hani
SH
Moussavi Nik
Esmaeil
E
Ebrahimie
Michael
M
Lardelli
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D008562:Membrane Glycoproteins; D029961:Zebrafish Proteins; C501106:ncln protein, zebrafish; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases