title: Deletion of small ankyrin 1 (sAnk1) isoforms results in structural and functional alterations in aging skeletal muscle fibers.
abstract: Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin 1 isoforms, of which sAnk1.5 is the most abundant. sAnk1 are localized in the sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, a myofibrillar protein. This interaction appears to contribute to stabilize the SR close to the myofibrils. Here we report the structural and functional characterization of skeletal muscles from sAnk1 knockout mice (KO). Deletion of sAnk1 did not change the expression and localization of SR proteins in 4- to 6-mo-old sAnk1 KO mice. Structurally, the main modification observed in skeletal muscles of adult sAnk1 KO mice (4-6 mo of age) was the reduction of SR volume at the sarcomere A band level. With increasing age (at 12-15 mo of age) extensor digitorum longus (EDL) skeletal muscles of sAnk1 KO mice develop prematurely large tubular aggregates, whereas diaphragm undergoes significant structural damage. Parallel functional studies revealed specific changes in the contractile performance of muscles from sAnk1 KO mice and a reduced exercise tolerance in an endurance test on treadmill compared with control mice. Moreover, reduced Qγ charge and L-type Ca(2+) current, which are indexes of affected excitation-contraction coupling, were observed in diaphragm fibers from 12- to 15-mo-old mice, but not in other skeletal muscles from sAnk1 KO mice. Altogether, these findings show that the ablation of sAnk1, by altering the organization of the SR, renders skeletal muscles susceptible to undergo structural and functional alterations more evident with age, and point to an important contribution of sAnk1 to the maintenance of the longitudinal SR architecture.
authors.affiliation: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; IIM-Interuniversity Institute of Myology;
authors.forename: E
authors.initials: E
authors.lastname: Giacomello
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padua, Italy;
authors.forename: M
authors.initials: M
authors.lastname: Quarta
authors.affiliation: Ce.S.I., Center for Research on Ageing and Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy; IIM-Interuniversity Institute of Myology;
authors.forename: C
authors.initials: C
authors.lastname: Paolini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence Italy; IIM-Interuniversity Institute of Myology;
authors.forename: R
authors.initials: R
authors.lastname: Squecco
authors.affiliation: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy;
authors.forename: P
authors.initials: P
authors.lastname: Fusco
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padua, Italy; IIM-Interuniversity Institute of Myology;
authors.forename: L
authors.initials: L
authors.lastname: Toniolo
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padua, Italy; IIM-Interuniversity Institute of Myology; Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Blaauw
authors.affiliation: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy;
authors.forename: L
authors.initials: L
authors.lastname: Formoso
authors.affiliation: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; IIM-Interuniversity Institute of Myology;
authors.forename: D
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine;
authors.forename: C
authors.initials: C
authors.lastname: Birkenmeier
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine;
authors.forename: L L
authors.initials: LL
authors.lastname: Peters
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence Italy; IIM-Interuniversity Institute of Myology;
authors.forename: F
authors.initials: F
authors.lastname: Francini
authors.affiliation: Ce.S.I., Center for Research on Ageing and Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy; IIM-Interuniversity Institute of Myology;
authors.forename: F
authors.initials: F
authors.lastname: Protasi
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padua, Italy; IIM-Interuniversity Institute of Myology; CNR-Neuroscience Institute, Padua, Italy; and.
authors.forename: C
authors.initials: C
authors.lastname: Reggiani
authors.affiliation: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; IIM-Interuniversity Institute of Myology; vincenzo.sorrentino@unisi.it.
authors.forename: V
authors.initials: V
authors.lastname: Sorrentino
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C491707:Ank1 protein, mouse; D017487:Ankyrins; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D020033:Protein Isoforms
keywords: aging; ankyrins; excitation-contraction coupling; myopathy; sarcoplasmic reticulum