SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.
ABCA1
SMA
SMN
cholesterol
plasma membrane
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
02 Feb 2023
02 Feb 2023
Historique:
received:
28
12
2022
revised:
20
01
2023
accepted:
31
01
2023
entrez:
11
2
2023
pubmed:
12
2
2023
medline:
15
2
2023
Statut:
epublish
Résumé
The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma membrane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.
Identifiants
pubmed: 36769246
pii: ijms24032916
doi: 10.3390/ijms24032916
pmc: PMC9917534
pii:
doi:
Substances chimiques
Transcription Factors
0
Membrane Proteins
0
Survival of Motor Neuron 1 Protein
0
ABCA1 protein, human
0
ATP Binding Cassette Transporter 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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