title: Spinophilin is required for normal morphology, Ca(2+) homeostasis and contraction but dispensable for β-adrenergic stimulation of adult cardiomyocytes.
abstract: Spinophilin (SPN) is a ubiquitously expressed scaffolding protein that interacts through several binding modules with a variety of target proteins. Thus, SPN bundles F-actin, targets protein phosphatase 1 to the ryanodine receptor, and targets regulators of G-protein signaling to G-protein coupled receptors in cardiomyocytes. In this work we studied the role of SPN on cardiomyocyte morphology, function, and β-adrenergic responsiveness using a homozygous SPN knock-out mouse model (SPN-/-). We show that spinophilin deficiency significantly (1) reduced cardiomyocyte length, (2) increases both Ca(2+) amplitude and maximal rate of Ca(2+) rise during systole, and (3) decreased shortening amplitude and maximal rate of shortening, while (4) β-adrenergic stimulation remained intact. Our data suggest that spinophilin is an upstream regulator required for normal growth and excitation-contraction coupling, but is dispensable for β-adrenergic stimulation of adult cardiomyocytes.
authors.affiliation: Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, 13092, Berlin, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Petzhold
authors.forename: André C
authors.initials: AC
authors.lastname: da Costa-Goncalves
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Ingo
authors.initials: I
authors.lastname: Morano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D019204:GTP-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011485:Protein Binding; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013599:Systole / Q000502:physiology; D000099273:Neurabins
chemical_list: D002118:Calcium; D019204:GTP-Binding Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine; D011943:Receptors, Adrenergic, beta; D000099273:Neurabins