title: Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ.
abstract: Myofilament regulation by protein kinases is well characterized, but relatively little is known about protein phosphatase control of myofilaments. Increased protein phosphatase type 1 (PP1) activity observed in failing hearts underscores the need for investigation of this intracellular signal, including the elements that regulate its activity. The Z-disc protein CapZ controls protein kinase C (PKC) regulation of cardiac myofilaments, but whether this effect is specific to PKC, or CapZ plays a general role in intracellular signalling, is not known. We sought to determine how the alpha isoform of PP1 (PP1alpha) regulates murine cardiac myofilaments and whether CapZ influences PP1alpha-dependent regulation of cardiac myofilaments. Immunoblot analysis showed PP1alpha binding to cardiac myofilaments. Exogenous PP1alpha increased myofilament Ca2+ sensitivity and maximal actomyosin Mg2+-ATPase activity while dephosphorylating myosin binding protein C, troponin T, troponin I, and myosin light chain 2. Extraction of CapZ decreased myofilament-associated PP1alpha and attenuated the effects of PP1alpha on myofilament activation. PP1alpha-dependent dephosphorylation of myofilament proteins was reduced with CapZ extraction, except for troponin I. Extracting CapZ after PP1alpha treatment allowed most of the PP1alpha-dependent effects on myofilament activation to remain, indicating that CapZ removal modestly desensitizes cardiac myofilaments to dephosphorylation. Our results demonstrate myofilament regulation by PP1alpha and support the concept that cardiac Z-discs are vital components in intracellular signalling.
authors: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors: Fenghua
authors: F
authors: Yang
authors: David L
authors: DL
authors: Aiello
authors: W Glen
authors: WG
authors: Pyle
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D051347:CapZ Actin Capping Protein / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051347:CapZ Actin Capping Protein; D000205:Actomyosin; D054645:Protein Phosphatase 1; D017301:Ca(2+) Mg(2+)-ATPase