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; Nilüfer Ertekin-Taner; Anders Nykjær; Olav M Andersen

doi:10.1016/j.neurobiolaging.2018.06.021

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, Nilüfer Ertekin-Taner, Anders Nykjær, Olav M Andersen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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 language	English
Journal	Neurobiology of Aging
Volume	71
Pages (from-to)	266.e11-266.e24
Number of pages	14
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.06.021
Publication status	Published - Nov 2018

Keywords

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

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10.1016/j.neurobiolaging.2018.06.021

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769419/pdf/nihms-1050600.pdf

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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., Ertekin-Taner, N., Nykjær, A., & Andersen, O. M. (2018). An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor. Neurobiology of Aging, 71, 266.e11-266.e24. https://doi.org/10.1016/j.neurobiolaging.2018.06.021

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

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.",

keywords = "Alternative transcription, Alzheimer's disease risk gene, Exon 30B, SORL1, SorLA",

author = "Jenny Blechingberg and Poulsen, {Annemarie Svane Aavild} and Mads Kj{\o}lby and Giulia Monti and Mariet Allen and Ivarsen, {Anne Kathrine} and Lincoln, {Sarah J} and Gangadaar Thotakura and V{\ae}gter, {Christian B} and Nil{\"u}fer Ertekin-Taner and Anders Nykj{\ae}r and Andersen, {Olav M}",

year = "2018",

month = nov,

doi = "10.1016/j.neurobiolaging.2018.06.021",

language = "English",

volume = "71",

pages = "266.e11--266.e24",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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Blechingberg, J , Poulsen, ASA , Kjølby, M, Monti, G, Allen, M, Ivarsen, AK, Lincoln, SJ, Thotakura, G, Vægter, CB, Ertekin-Taner, N, Nykjær, A & Andersen, OM 2018, 'An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor', Neurobiology of Aging, vol. 71, pp. 266.e11-266.e24. https://doi.org/10.1016/j.neurobiolaging.2018.06.021

An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor. / Blechingberg, Jenny ; Poulsen, Annemarie Svane Aavild ; Kjølby, Mads et al.
In: Neurobiology of Aging, Vol. 71, 11.2018, p. 266.e11-266.e24.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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

U2 - 10.1016/j.neurobiolaging.2018.06.021

DO - 10.1016/j.neurobiolaging.2018.06.021

M3 - Journal article

C2 - 30078640

SN - 0197-4580

VL - 71

SP - 266.e11-266.e24

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

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Keywords

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