Transportin 3 (TNPO3) and related proteins in limb girdle muscular dystrophy D2 muscle biopsies: A morphological study and pathogenetic hypothesis.

Abstract

LGMD D2 is a disease caused by TNPO3 mutation. We describe the expression of TNPO3 and selected proteins, likely modified by TNPO3 mutation, in muscle biopsies of affected patients. We also aim to find other genes involved in pathways correlated to TNPO3. Our morphological study on LGMD D2 muscle described the expression of TNPO3 and SRSF1, a splicing factor transported by TNPO3. Moreover, we investigated some sarcomeric and nuclear proteins, likely altered by TNPO3 mutation. Through an in silico approach we tried to identify genes involved in pathways that include, besides TNPO3 and SRSF1, p62 and Murf-1, altered in LGMD D2. In patients' muscles TNPO3 appeared weaker and randomly organized, with sporadic cytoplasmic aggregates positive for TNPO3; both SRSF1 and sarcomeric alpha actinin showed a different expression, while there were no alterations in the expression of the nuclear proteins. The in silico study lead to identify five genes, all coding for proteins responsible for muscle contraction. Our data suggest a possible interference in the morphology and function of myofibrillar network by mutated TNPO3; these findings are supported by the in silico identification of genes involved in muscle contraction that could help to explain the pathogenic mechanisms of LGMD D2.

• Authors: Roberta Costa, Maria Teresa Rodia, Sara Vianello, Spartaco Santi, Giovanna Lattanzi, Corrado Angelini, Elena Pegoraro, Giovanna Cenacchi
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 30 Issue 8 Pg. 685-692 (08 2020) ISSN: 1873-2364 [Electronic] England
• PMID: 32690349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Muscle Proteins
• Nuclear Proteins
• TNPO3 protein, human
• Tripartite Motif Proteins
• beta Karyopherins
• TRIM63 protein, human
• Ubiquitin-Protein Ligases

Topics

• Biopsy
• Computer Simulation
• Exome
• Female
• Humans
• In Vitro Techniques
• Muscle Proteins
• Muscles (pathology)
• Muscular Dystrophies, Limb-Girdle (genetics, pathology)
• Mutation (genetics)
• Nuclear Proteins (genetics)
• Tripartite Motif Proteins
• Ubiquitin-Protein Ligases
• beta Karyopherins (genetics)