Protein Kinase A, Ca2+/Calmodulin-Dependent Kinase II, and Calcineurin Regulate the Intracellular Trafficking of Myopodin between the Z-Disc and the Nucleus of Cardiac Myocytes
| Autor: | Ashwini Dhume, Alison D. Schecter, Christian Faul, Peter Mundel |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Calcineurin Inhibitors
Active Transport Cell Nucleus A Kinase Anchor Proteins Muscle Proteins Biology Binding Competitive Cell Line Myoblasts Mice Phosphoserine Ca2+/calmodulin-dependent protein kinase Animals Humans Actinin Myocytes Cardiac Nuclear protein Protein kinase A education Molecular Biology Adaptor Proteins Signal Transducing Cell Nucleus education.field_of_study Calcineurin Microfilament Proteins Nuclear Proteins Articles Cell Biology Cyclic AMP-Dependent Protein Kinases Rats Cell biology Enzyme Activation Cytoskeletal Proteins Protein Transport Phosphothreonine Myomegalin 14-3-3 Proteins Phosphorylation Signal transduction Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Binding Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 27:8215-8227 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00950-07 |
| Popis: | Spatial and temporal resolution of intracellular signaling can be achieved by compartmentalizing transduction units. Myopodin is a dual-compartment, actin-bundling protein that shuttles between the nucleus and the Z-disc of myocytes in a differentiation- and stress-dependent fashion. Importin alpha binding and nuclear import of myopodin are regulated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3. Here we show that in the heart myopodin forms a Z-disc signaling complex with alpha-actinin, calcineurin, Ca2+/calmodulin-dependent kinase II (CaMKII), muscle-specific A-kinase anchoring protein, and myomegalin. Phosphorylation of myopodin by protein kinase A (PKA) or CaMKII mediates 14-3-3 binding and nuclear import in myoblasts. Dephosphorylation of myopodin by calcineurin abrogates 14-3-3beta binding. Activation of PKA or inhibition of calcineurin in adult cardiac myocytes releases myopodin from the Z-disc and induces its nuclear import. The identification of myopodin as a direct target of PKA, CaMKII, and calcineurin defines a novel intracellular signaling pathway whereby changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart. |
| Databáze: | OpenAIRE |
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