Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase.
Subcellular targeting of the components of the cAMP-dependent pathway is thought to be essential for intracellular signaling. Here we have identified a novel protein, named myomegalin, that interacts with the cyclic nucleotide phosphodiesterase PDE4D, thereby targeting it to particulate structures. Myomegalin is a large 2,324-amino acid protein mostly composed of alpha-helical and coiled-coil structures, with domains shared with microtubule-associated proteins, and a leucine zipper identical to that found in the Drosophila centrosomin. Transcripts of 7.5-8 kilobases were present in most tissues, whereas a short mRNA of 2.4 kilobases was detected only in rat testis. A third splicing variant was expressed predominantly in rat heart. Antibodies against the deduced sequence recognized particulate myomegalin proteins of 62 kDa in testis and 230-250 kDa in heart and skeletal muscle. Immunocytochemistry and transfection studies demonstrate colocalization of PDE4D and myomegalin in the Golgi/centrosomal area of cultured cells, and in sarcomeric structures of skeletal muscle. Myomegalin expressed in COS-7 cells coimmunoprecipitated with PDE4D3 and sequestered it to particulate structures. These findings indicate that myomegalin is a novel protein that functions as an anchor to localize components of the cAMP-dependent pathway to the Golgi/centrosomal region of the cell.
Verde
I
I
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, California 94305-5317, USA.
Pahlke
G
G
Salanova
M
M
Zhang
G
G
Wang
S
S
Coletti
D
D
Onuffer
J
J
Jin
S L
SL
Conti
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D004330:Drosophila; D006056:Golgi Apparatus / Q000378:metabolism*; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011485:Protein Binding; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae; D017421:Sequence Analysis
D008869:Microtubule-Associated Proteins; C426025:Pde4dip protein, rat; D011506:Proteins; D015105:3',5'-Cyclic-AMP Phosphodiesterases