SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.

Autor: Gabanella F; CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy., Onori A; CNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy., Pisani C; CNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy., Fiore M; CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy., Ferraguti G; Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy., Colizza A; Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy., de Vincentiis M; Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy., Ceccanti M; Center for Rare Neuromuscular Diseases, Department of Human Neuroscience, Policlinico Umberto I, Sapienza University of Rome, 00185 Rome, Italy., Inghilleri M; Center for Rare Neuromuscular Diseases, Department of Human Neuroscience, Policlinico Umberto I, Sapienza University of Rome, 00185 Rome, Italy., Corbi N; CNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy., Passananti C; CNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy., Di Certo MG; CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Feb 02; Vol. 24 (3). Date of Electronic Publication: 2023 Feb 02.
DOI: 10.3390/ijms24032916
Abstrakt: 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.
Databáze: MEDLINE
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