An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor.
Neurobiol Aging
; 71: 266.e11-266.e24, 2018 11.
Article
de En
| MEDLINE
| ID: mdl-30078640
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines de transport membranaire
/
Encéphale
/
Protéines apparentées au récepteur LDL
/
Maladie d'Alzheimer
Type d'étude:
Etiology_studies
/
Risk_factors_studies
Limites:
Aged
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Neurobiol Aging
Année:
2018
Type de document:
Article
Pays d'affiliation:
Danemark