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Advisor(s)
Abstract(s)
Subcellular targeting of the components of the cAMPdependent
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 a-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.