Myomegalin is a Novel Protein of the Golgi/Centrosome That Interacts with a Cyclic Nucleotide Phosphodiesterase

Ignacio Verde, Gudrun Pahlke, Michele Salanova, Gu Zhang, Sonya Wang, Dario Coletti, James Onuffer, S. L.Catherine Jin, Marco Conti

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)11189-11198
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number14
DOIs
StatePublished - Apr 6 2001
Externally publishedYes

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    Verde, I., Pahlke, G., Salanova, M., Zhang, G., Wang, S., Coletti, D., Onuffer, J., Jin, S. L. C., & Conti, M. (2001). Myomegalin is a Novel Protein of the Golgi/Centrosome That Interacts with a Cyclic Nucleotide Phosphodiesterase. Journal of Biological Chemistry, 276(14), 11189-11198. https://doi.org/10.1074/jbc.M006546200