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001-es BibID:	BIBFORM121062
035-os BibID:	(Scopus)85192031398
Első szerző:	Gasperi, Rita De
Cím:	Septin 7 interacts with Numb to preserve sarcomere structural organization and muscle contractile function / Rita De Gasperi, Laszlo Csernoch, Beatrix Dienes, Monika Gonczi, Jayanta K. Chakrabarty, Shahar Goeta, Abdurrahman Aslan, Carlos A Toro, David Karasik, Lewis M. Brown, Marco Brotto, Christopher P. Cardozo
Dátum:	2024
ISSN:	2050-084X
Megjegyzések:	Here, we investigated the mechanisms by which aging-related reductions of the levels of Numb in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development, including asymmetric cell division, cell-type specification, and termination of intracellular signaling. Numb expression is reduced in old humans and mice. We previously showed that, in mouse skeletal muscle fibers, Numb is localized to sarcomeres where it is concentrated near triads; conditional inactivation of Numb and a closely related protein Numb-like (Numbl) in mouse myofibers caused weakness, disorganization of sarcomeres, and smaller mitochondria with impaired function. Here, we found that a single knockout of Numb in myofibers causes reduction in tetanic force comparable to a double Numb, Numbl knockout. We found by proteomics analysis of protein complexes isolated from C2C12 myotubes by immunoprecipitation using antibodies against Numb that Septin 7 is a potential Numb-binding partner. Septin 7 is a member of the family of GTP-binding proteins that organize into filaments, sheets, and rings, and is considered part of the cytoskeleton. Immunofluorescence evaluation revealed a partial overlap of staining for Numb and Septin 7 in myofibers. Conditional, inducible knockouts of Numb led to disorganization of Septin 7 staining in myofibers. These findings indicate that Septin 7 is a Numb-binding partner and suggest that interactions between Numb and Septin 7 are critical for structural organization of the sarcomere and muscle contractile function.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk animals metabolism mice genetics Intracellular Signaling Peptides and Proteins signal peptide Membrane Proteins physiology skeletal muscle Protein Binding Muscle Contraction skeletal CYTOSKELETON knockout mouse Nerve Tissue Proteins nerve protein knockout CELL BIOLOGY Muscle Fibers sarcomere Septins skeletal muscle cell Excitation-contraction coupling numb septin sarcomere structure NUMB protein sept7 protein
Megjelenés:	eLife. - 12 (2024), p. RP89424. -
További szerzők:	Csernoch László (1961-) (élettanász) Dienes Beatrix (1972-) (élettanász, molekuláris biológus) Gönczi Mónika (1974-) (élettanász) Chakrabarty, Jayanta K. Goeta, Shahar Aslan, Abdurrahman Toro, Carlos A. Karasik, David Brown, Lewis M. Brotto, Marco Cardozo, Christopher P.
Pályázati támogatás:	2020-4.1.1-TKP2020 Egyéb K_137600 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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