Related Experiment Video
Updated: Aug 19, 2026
Immunolabelling Myofiber Degeneration in Muscle Biopsies
Published on: December 5, 2019
Protein 4.1R expression in normal and dystrophic skeletal muscle
François Delhommeau1, Nicole Dalla Venezia, Madeleine Morinière
1Inserm U473 & Service d'hématologie, hôpital de Bicêtre and faculté de médecine Paris-Sud, 63, rue Gabriel-Péri, 94270 Le Kremlin-Bicêtre cedex, France.
Abstract:
4.1R pre-mRNA alternative splicing results in multiple mRNA and protein isoforms that are expressed in virtually all tissues. More specifically, isoforms containing the alternative exon 17a, are exclusively expressed in muscle tissues. In this report, we show that these isoforms are preferentially present in the myoplasm of fast myofibres. 4.1R epitopes are also found at the sarcolemma of both slow and fast myofibres in normal muscle. Interestingly, they are absent from dystrophin-deficient sarcolemma of DMD muscle, and colocalize with partially expressed dystrophin in BMD muscle. We also show that alternative splicing of exons 16 and 17a is regulated during muscle differentiation in an asynchronous fashion, with an early inclusion of exon 16 in forming myotubes, and a late inclusion of exon 17a. Consistently, Western blot analysis led to characterize mainly an approximately 96/98-kDa doublet bearing exons 16-17a-encoding peptide, exclusively occurring in the differentiated muscle.
Insights
Protein 4.1R isoforms containing exon 17a are specific to muscle tissue and localize to myofibers. Their presence at the sarcolemma is linked to dystrophin in muscular dystrophy models.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Alternative splicing of 4.1R pre-mRNA generates diverse mRNA and protein isoforms.
- Specific isoforms containing exon 17a are exclusively found in muscle tissues.
Purpose of the Study:
- To investigate the localization and regulation of 4.1R isoforms in muscle.
- To examine the relationship between 4.1R and dystrophin in muscle pathology.
Main Methods:
- Immunohistochemistry to detect 4.1R epitopes in muscle.
- Analysis of alternative splicing during muscle differentiation.
- Western blot to characterize 4.1R protein isoforms.
Main Results:
- 4.1R isoforms with exon 17a are preferentially located in the myoplasm of fast myofibers.
- 4.1R epitopes are present at the sarcolemma of normal muscle but absent in Duchenne muscular dystrophy (DMD) muscle.
- Alternative splicing of exons 16 and 17a is asynchronous during muscle differentiation.
- A specific 96/98-kDa 4.1R protein doublet containing exons 16-17a is found exclusively in differentiated muscle.
Conclusions:
- Muscle-specific 4.1R isoforms are regulated during differentiation and localized within myofibers.
- The association of 4.1R with the sarcolemma is dependent on dystrophin, suggesting a role in muscle integrity.
Related Concept Videos
01:21Satellite Stem Cells and Muscular Dystrophy
01:13Formation of Muscle Fibers from Myoblasts
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...