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Cells 2018, 7(10), 170; https://doi.org/10.3390/cells7100170

Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy

1
CNR Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy
2
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
3
Laboratory of Musculoskeletal Cell Biology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
4
KTH, Science for Life Laboratory, SE 171 65 Solna, Sweden
5
Endocrinology Unit, Department of Medical & Surgical Sciences, Alma Mater Studiorum University of Bologna, S Orsola-Malpighi Hospital, 40138 Bologna, Italy
6
Department of Biochemistry and Biophysics (DBB), Stockholm University, SE-106 91 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Received: 16 August 2018 / Revised: 1 October 2018 / Accepted: 11 October 2018 / Published: 15 October 2018
(This article belongs to the Collection Lamins and Laminopathies)
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Abstract

LMNA linked-Emery-Dreifuss muscular dystrophy (EDMD2) is a rare disease characterized by muscle weakness, muscle wasting, and cardiomyopathy with conduction defects. The mutated protein lamin A/C binds several nuclear envelope components including the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the inner nuclear membrane protein Samp1 (Spindle Associated Membrane Protein 1). Considering that Samp1 is upregulated during muscle cell differentiation and it is involved in nuclear movement, we hypothesized that it could be part of the protein platform formed by LINC proteins and prelamin A at the myotube nuclear envelope and, as previously demonstrated for those proteins, could be affected in EDMD2. Our results show that Samp1 is uniformly distributed at the nuclear periphery of normal human myotubes and committed myoblasts, but its anchorage at the nuclear poles is related to the presence of farnesylated prelamin A and it is disrupted by the loss of prelamin A farnesylation. Moreover, Samp1 is absent from the nuclear poles in EDMD2 myotubes, which shows that LMNA mutations associated with muscular dystrophy, due to reduced prelamin A levels in muscle cell nuclei, impair Samp1 anchorage. Conversely, SUN1 pathogenetic mutations do not alter Samp1 localization in myotubes, which suggests that Samp1 lies upstream of SUN1 in nuclear envelope protein complexes. The hypothesis that Samp1 is part of the protein platform that regulates microtubule nucleation from the myotube nuclear envelope in concert with pericentrin and LINC components warrants future investigation. As a whole, our data identify Samp1 as a new contributor to EDMD2 pathogenesis and our data are relevant to the understanding of nuclear clustering occurring in laminopathic muscle. View Full-Text
Keywords: Emery-Dreifuss Muscular Dystrophy type 2 (EDMD2); Samp1 (NET5); prelamin A; LINC complex; myonuclear positioning Emery-Dreifuss Muscular Dystrophy type 2 (EDMD2); Samp1 (NET5); prelamin A; LINC complex; myonuclear positioning
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Mattioli, E.; Columbaro, M.; Jafferali, M.H.; Schena, E.; Hallberg, E.; Lattanzi, G. Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy. Cells 2018, 7, 170.

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