An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor

Jenny Blechingberg, Annemarie Svane Aavild Poulsen, Mads Kjølby, Giulia Monti, Mariet Allen, Anne Kathrine Ivarsen, Sarah J. Lincoln, Gangadaar Thotakura, Christian B. Vægter, Nilufer Taner, Anders Nykjær, Olav M. Andersen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

SORL1 encodes a 250-kDa protein named sorLA, a functional sorting receptor for the amyloid precursor protein (APP). Several single nucleotide polymorphisms of the gene SORL1, encoding sorLA, are genetically associated with Alzheimer's disease (AD). In the existing literature, SORL1 is insufficiently described at the transcriptional level, and there is very limited amount of functional data defining different transcripts. We have characterized a SORL1 transcript containing a novel exon 30B. The transcript is expressed in most brain regions with highest expression in the temporal lobe and hippocampus. Exon 30B is spliced to exon 31, leading to a mature transcript that encodes an 829 amino acid sorLA receptor. This receptor variant lacks the binding site for APP and is unlikely to function in APP sorting. This transcript is expressed in equal amounts in the cerebellum from AD and non-AD individuals. Our data describe a transcript that encodes a truncated sorLA receptor, suggesting novel neuronal functions for sorLA and that alternative transcription provides a mechanism for SORL1 activity regulation.

Original languageEnglish (US)
JournalNeurobiology of Aging
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Alternative transcription
  • Alzheimer's disease risk gene
  • Exon 30B
  • SORL1
  • SorLA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Blechingberg, J., Poulsen, A. S. A., Kjølby, M., Monti, G., Allen, M., Ivarsen, A. K., Lincoln, S. J., Thotakura, G., Vægter, C. B., Taner, N., Nykjær, A., & Andersen, O. M. (Accepted/In press). An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor. Neurobiology of Aging. https://doi.org/10.1016/j.neurobiolaging.2018.06.021