title: Skeletal muscle expression of the adhesion-GPCR CD97: CD97 deletion induces an abnormal structure of the sarcoplasmatic reticulum but does not impair skeletal muscle function.
abstract: CD97 is a widely expressed adhesion class G-protein-coupled receptor (aGPCR). Here, we investigated the presence of CD97 in normal and malignant human skeletal muscle as well as the ultrastructural and functional consequences of CD97 deficiency in mice. In normal human skeletal muscle, CD97 was expressed at the peripheral sarcolemma of all myofibers, as revealed by immunostaining of tissue sections and surface labeling of single myocytes using flow cytometry. In muscle cross-sections, an intracellular polygonal, honeycomb-like CD97-staining pattern, typical for molecules located in the T-tubule or sarcoplasmatic reticulum (SR), was additionally found. CD97 co-localized with SR Ca2+-ATPase (SERCA), a constituent of the longitudinal SR, but not with the receptors for dihydropyridine (DHPR) or ryanodine (RYR), located in the T-tubule and terminal SR, respectively. Intracellular expression of CD97 was higher in slow-twitch compared to most fast-twitch myofibers. In rhabdomyosarcomas, CD97 was strongly upregulated and in part more N-glycosylated compared to normal skeletal muscle. All tumors were strongly CD97-positive, independent of the underlying histological subtype, suggesting high sensitivity of CD97 for this tumor. Ultrastructural analysis of murine skeletal myofibers confirmed the location of CD97 in the SR. CD97 knock-out mice had a dilated SR, resulting in a partial increase in triad diameter yet not affecting the T-tubule, sarcomeric, and mitochondrial structure. Despite these obvious ultrastructural changes, intracellular Ca2+ release from single myofibers, force generation and fatigability of isolated soleus muscles, and wheel-running capacity of mice were not affected by the lack of CD97. We conclude that CD97 is located in the SR and at the peripheral sarcolemma of human and murine skeletal muscle, where its absence affects the structure of the SR without impairing skeletal muscle function.
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zyryanova
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Rick
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Heart Center Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Sittig
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kerner
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ruffert
authors.affiliation: Clinic for Trauma and Reconstructive Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Glasmacher
authors.affiliation: Clinic for Trauma and Reconstructive Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hepp
authors.affiliation: Institute of Anatomy, University of Leipzig, Leipzig, Germany.
authors.forename: Karla
authors.initials: K
authors.lastname: Punkt
authors.affiliation: Clinic of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D043562:Receptors, G-Protein-Coupled; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D020746:Calcium Channels, L-Type; D043562:Receptors, G-Protein-Coupled; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine