Identification and mapping of protein kinase A binding sites in the costameric protein myospryn.
Recently we identified a novel target gene of MEF2A named myospryn that encodes a large, muscle-specific, costamere-restricted alpha-actinin binding protein. Myospryn belongs to the tripartite motif (TRIM) superfamily of proteins and was independently identified as a dysbindin-interacting protein. Dysbindin is associated with alpha-dystrobrevin, a component of the dystrophin-glycoprotein complex (DGC) in muscle. Apart from these initial findings little else is known regarding the potential function of myospryn in striated muscle. Here we reveal that myospryn is an anchoring protein for protein kinase A (PKA) (or AKAP) whose closest homolog is AKAP12, also known as gravin/AKAP250/SSeCKS. We demonstrate that myospryn co-localizes with RII alpha, a type II regulatory subunit of PKA, at the peripheral Z-disc/costameric region in striated muscle. Myospryn interacts with RII alpha and this scaffolding function has been evolutionarily conserved as the zebrafish ortholog also interacts with PKA. Moreover, myospryn serves as a substrate for PKA. These findings point to localized PKA signaling at the muscle costamere.
Reynolds
Joseph G
JG
Department of Biology, Program in Cell and Molecular Biology, Boston University, 24 Cummington Street, Boston, MA 02215, USA.
McCalmon
Sarah A
SA
Tomczyk
Thomas
T
Naya
Francisco J
FJ
D054758:A Kinase Anchor Proteins; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D010449:Peptide Mapping; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D054758:A Kinase Anchor Proteins; C491161:Akap12 protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C484938:Cmya5 protein, mouse; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; C517821:Prkar2a protein, mouse; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases