Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin

Author:

Fontelonga Tatiana1ORCID,Hall Arielle J.1ORCID,Brown Jaedon L.1,Jung Youngsook L.1ORCID,Alexander Matthew S.23,Dominov Janice A.4ORCID,Mouly Vincent5ORCID,Vieira Natassia6ORCID,Zatz Mayana7ORCID,Vainzof Mariz7ORCID,Gussoni Emanuela18ORCID

Affiliation:

1. Division of Genetics and Genomics Boston Children's Hospital 300 Longwood Avenue Boston MA 02115 USA

2. Department of Pediatrics Division of Neurology at Children's of Alabama 1900 University Blvd Birmingham AL 35294 USA

3. Department of Genetics University of Alabama at Birmingham 1900 University Avenue Birmingham AL 35294 USA

4. Department of Neurology University of Massachusetts 368 Plantation Street Worcester MA 01605 USA

5. Center for research In Myology Institute de Myologie/Myology Institute UMRS 974 Sorbonne Université‐INSERM Batiment Babinski, GH Pitié‐Salpétrière 47 bd de l'Hôpital Paris Cedex 13 75651 France

6. Stemcorp R. Mato Grosso, 306 Higienópolis, São Paulo 01239‐040 Brazil

7. Human Genome and Stem Cells Research Center Biosciences Institute University of São Paulo R. do Matão, 277 Butantã, São Paulo 05508‐090 Brazil

8. The Stem Cell Program Boston Children's Hospital 300 Longwood Avenue Boston MA 02115 USA

Abstract

AbstractTetraspanins organize protein complexes at the cell membrane and are responsible for assembling diverse binding partners in changing cellular states. Tetraspanin CD82 is a useful cell surface marker for prospective isolation of human myogenic progenitors and its expression is decreased in Duchenne muscular dystrophy (DMD) cell lines. The function of CD82 in skeletal muscle remains elusive, partly because the binding partners of this tetraspanin in muscle cells have not been identified. CD82‐associated proteins are sought to be identified in human myotubes via mass spectrometry proteomics, which identifies dysferlin and myoferlin as CD82‐binding partners. In human dysferlinopathy (Limb girdle muscular dystrophy R2, LGMDR2) myogenic cell lines, expression of CD82 protein is near absent in two of four patient samples. In the cell lines where CD82 protein levels are unaffected, increased expression of the ≈72 kDa mini‐dysferlin product is identified using an antibody recognizing the dysferlin C‐terminus. These data demonstrate that CD82 binds dysferlin/myoferlin in differentiating muscle cells and its expression can be affected by loss of dysferlin in human myogenic cells.

Funder

National Institutes of Health

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

Wiley

Subject

General Medicine

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