TY - JOUR
T1 - An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor
AU - Blechingberg, Jenny
AU - Poulsen, Annemarie Svane Aavild
AU - Kjølby, Mads
AU - Monti, Giulia
AU - Allen, Mariet
AU - Ivarsen, Anne Kathrine
AU - Lincoln, Sarah J.
AU - Thotakura, Gangadaar
AU - Vægter, Christian B.
AU - Ertekin-Taner, Nilüfer
AU - Nykjær, Anders
AU - Andersen, Olav M.
N1 - Funding Information:
This work was supported by grants from The Lundbeck Foundation [R248-2017-431, DANDRITE-R248-2016-2518], The Danish National Research Foundation [DNRF133], The Novo Nordisk Foundation, The Augustinus Foundation, The Hartmann Foundation, The Henrik Henriksen Foundation, The Oda and Hans Svenningsen Foundation, and The Danish Council for Independent Research | Medical Sciences DFF [4004-00371 and 7016-00261]. This work was also supported by the National Institute on Aging [U01 AG046139 and RF1 AG051504], National Institute of Neurological Disorders and Stroke [R01 NS080820] and Bright Focus Foundation [27J-01-03] awarded to N.E.-T. The authors are grateful for expert technical assistance by Sandra Bonnesen.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - Alternative transcription
KW - Alzheimer's disease risk gene
KW - Exon 30B
KW - SORL1
KW - SorLA
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U2 - 10.1016/j.neurobiolaging.2018.06.021
DO - 10.1016/j.neurobiolaging.2018.06.021
M3 - Article
C2 - 30078640
AN - SCOPUS:85050856105
SN - 0197-4580
VL - 71
SP - 266.e11-266.e24
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -