Key points are not available for this paper at this time.
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 theDrosophila 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. 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 theDrosophila 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. protein kinase A A kinase anchoring protein phosphodiesterase kilobase pair(s) base pair(s) open reading frame reverse transcriptase polymerase chain reaction activation domain 3-amino-1,2,4,-triazole polyacrylamide gel electrophoresis selection medium phosphate-buffered saline Tris-buffered saline with Tween 20 amino acid(s) 4-morpholinepropanesulfonic acid radioimmune precipitation assay Only in recent years has it been realized that the components of the signal transduction machinery are organized in macromolecular complexes located in close proximity to the plasma membrane or in discrete subcellular structures. These complexes are assembled by scaffold proteins often devoid of enzymatic activity and for the sole function of bringing together different signaling molecules (1Cohen G.B. Ren R. Baltimore D. Cell. 1995; 80: 237-248Abstract Full Text PDF PubMed Scopus (924) Google Scholar, 2Mochly-Rosen D. Science. 1995; 268: 247-251Crossref PubMed Scopus (832) Google Scholar). These signaling/scaffold protein complexes are necessary and often indispensable for signaling, as disruption or blocking the formation of these complexes decreases the efficiency of signaling or negates it altogether.Even though cAMP is a diffusible second messenger, the enzymes involved in this signaling pathway are targeted to different subcellular compartments. With few exceptions, adenylyl cyclases are plasma membrane-associated proteins, and protein kinase A (PKA),1 one of the effectors of cAMP signaling, is anchored to discrete structures within the cell via regulatory subunit interaction with A kinase anchoring proteins (AKAPs) (3Rubin C.S. Biochim. Biophys. Acta. 1994; 1224: 467-479PubMed Google Scholar, 4Colledge M. Scott J.D. Trends Cell Biol. 1999; 9: 216-221Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar). Several different AKAPs that function as scaffold proteins have been characterized. For instance, AKAP79 is part of a multicomplex, which, in addition to the PKA regulatory subunit RII, includes protein kinase C and the phosphatase PP2B/calcineurin (5Coghlan V.M. Perrino B.A. Howard M. Langeberg L.K. Hicks J.B. Gallatin W.M. Scott J.D. Science. 1995; 267: 108-111Crossref PubMed Scopus (524) Google Scholar). Disruption of the PKA interaction with AKAPs abolishes the cAMP-dependent regulation of ion channels (6Rosenmund C. Carr D.W. Bergeson S.E. Nilaver G. Scott J.D. Westbrook G.L. Nature. 1994; 368: 853-856Crossref PubMed Scopus (322) Google Scholar, 7Johnson B.D. Scheuer T. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 11492-11496Crossref PubMed Scopus (157) Google Scholar). PKA regulatory subunits have also been localized in the centrosome in culture cells (8Nigg E.A. Hilz H. Eppenberger H.M. Dutly F. EMBO J. 1985; 4: 2801-2806Crossref PubMed Scopus (197) Google Scholar), and in cells of the central nervous system (9De Camilli P. Moretti M. Donini S.D. Walter U. Lohmann S.M. J. Cell Biol. 1986; 103: 189-203Crossref PubMed Scopus (144) Google Scholar), thus opening the possibility that microenvironments of cAMP signaling may be necessary for intracellular trafficking and organelle movements during cell replication.Cyclic nucleotide phosphodiesterases, the enzymes that degrade and inactivate cAMP, may play an important role in signaling compartmentalization by controlling cAMP diffusion to the PKA anchored to different the of present in a cell 1995; PubMed Scopus Google Scholar, M. Biol. 1999; PubMed Google Scholar, M. G. C. 1995; PubMed Scopus Google Scholar, M. G.B. PubMed Scopus Google Scholar), are in the particulate of the and have been to different compartments. and have that the PDE4D are particulate or the amino present in the protein G.B. S. G. R. C. J. PubMed Scopus Google Scholar, S. M. T. F. C. M. M. PubMed Scopus Google Scholar, T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), and are located in different subcellular as by cells, and with amino are in the particulate and are localized in a region to structures, as as to the membrane region T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). a third variant the of is is mostly in the and by cAMP is with in these cells T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of PDE4D in discrete subcellular structures has also been in S. Cell Biophys. PubMed Scopus Google Scholar). These findings open the possibility that the subcellular of PDE4D is and this may be during cAMP the of subcellular we to proteins that with these PDE4D and to anchor to different Here we the of a novel protein named myomegalin, is a of skeletal and is expressed in cells in cells it is targeted to the Golgi/centrosomal myomegalin in the in heart and skeletal muscle. protein with PDE4D in the cells and these we the and the of myomegalin, a novel protein with the of a splicing of myomegalin detected in rat may functions in and Myomegalin is targeted to the Golgi/centrosomal region in cultured COS-7 and cells and in cells of the whereas in and skeletal it is with the or the that one of the functions of this protein is in cAMP signaling compartmentalization it a of the cAMP signaling to these subcellular is to the was identified for by or 1995; Google and is mostly composed of coiled-coil structures with leucine zipper leucine zipper the amino is to the only leucine zipper found in one variant of in coiled-coil structures is also shared and is a of the and the 1999; Google and is thought to play a role during of the central nervous system and 1995; Google Scholar). A of has been in J. Cell Biol. PubMed Scopus Google Scholar). that the and of the a a splicing variant of the myomegalin is expressed in cells of rat testis and is localized in a Golgi/centrosomal region of and it be it is located in the of the it is that the myomegalin has functions during that with of the be that proteins to the have been These A and and protein G. C. D. J. Cell Sci. Google Scholar, C. G. A. P. H. D. J. Cell Sci. Google Scholar, Cell Biol. PubMed Scopus Google Scholar). to the protein is and myomegalin is to to these function of is present large coiled-coil proteins localized in the have been as a of proteins S. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, C. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar). the and proteins have coiled-coil and a domain the that targeting Myomegalin is to in coiled-coil a domain to the domain be identified the of myomegalin, though the amino of this protein are to it to the of an interaction of PDE4D with the myomegalin was by the of the protein, we have of an interaction of the myomegalin variant with of indicate that the proteins may in a in the cell. addition to the interaction detected with the the variant of myomegalin and PDE4D in a of myomegalin targeted the PDE4D3 to the particulate of COS-7 myomegalin and PDE4D were in cultured cells as as in and skeletal of PDE4D that a of interaction with myomegalin is in a domain that to the amino of the region domain is in the of opening the possibility that may with domain of PDE4D of a region of α-helical with of the of myomegalin also α-helical domains that may the interaction with a the we have that this PDE4D interacts with myomegalin, is also involved in with the regulatory domain and that it functions as an domain that the activity of the J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). it is the interaction and the to myomegalin are or the is it the of myomegalin the activity of the have that of PDE4D3 the interaction of this domain with the amino J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google it is that the of also the of the PDE4D to with studies are to this is that the interaction of PDE4D with myomegalin, and with the may be a and that of this protein may during signaling. have been that PDE4D3 may activation of the protein kinase pathway H. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google of coiled-coil it is that myomegalin with or interacts with of a leucine zipper is also to is with this addition to a proteins may be with a domain to the domain involved in a found in and an domain that an were the of these domains that myomegalin is present in a with proteins, may be involved in or with interaction with structures. the possibility that myomegalin may play a role in the different of the is expressed in skeletal and an important function in with a myomegalin a was in the region or in the be PDE4D and myomegalin are in the or are with the Several transduction proteins have been localized in the region of the adenylyl and the regulatory subunit of PKA T. J. Biol. Full Text Full Text PDF PubMed Scopus Google J. M. J. Cell Biol. PubMed Scopus Google Scholar). it is that myomegalin PDE4D to a in the cAMP signaling in colocalization of PDE4D and myomegalin in Golgi/centrosomal structures to a role of cyclic nucleotide signaling in the function of these of a to the may have an important function in controlling cAMP diffusion to these PKA regulatory and anchoring have also been localized in the and in the centrosome (8Nigg E.A. Hilz H. Eppenberger H.M. Dutly F. EMBO J. 1985; 4: 2801-2806Crossref PubMed Scopus (197) Google Scholar, Camilli P. Moretti M. Donini S.D. Walter U. Lohmann S.M. J. Cell Biol. 1986; 103: 189-203Crossref PubMed Scopus (144) Google Scholar, G. Lohmann S.M. M. Cell PubMed Scopus Google G. M. T. S. EMBO J. 1999; PubMed Scopus Google Scholar). findings that PDE4D in these to the of activation of and the in these role of cAMP signaling in centrosome function and in in the is though is that cAMP as as T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. A. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). is by cAMP J. Cell Biol. PubMed Scopus Google Scholar), and cyclic have been in the of movements Biol. Cell. PubMed Scopus Google Scholar). it is that of a in these via myomegalin interaction may be involved in the of organelle movements or Only in recent years has it been realized that the components of the signal transduction machinery are organized in macromolecular complexes located in close proximity to the plasma membrane or in discrete subcellular structures. These complexes are assembled by scaffold proteins often devoid of enzymatic activity and for the sole function of bringing together different signaling molecules (1Cohen G.B. Ren R. Baltimore D. Cell. 1995; 80: 237-248Abstract Full Text PDF PubMed Scopus (924) Google Scholar, 2Mochly-Rosen D. Science. 1995; 268: 247-251Crossref PubMed Scopus (832) Google Scholar). These signaling/scaffold protein complexes are necessary and often indispensable for signaling, as disruption or blocking the formation of these complexes decreases the efficiency of signaling or negates it though cAMP is a diffusible second messenger, the enzymes involved in this signaling pathway are targeted to different subcellular compartments. With few exceptions, adenylyl cyclases are plasma membrane-associated proteins, and protein kinase A (PKA),1 one of the effectors of cAMP signaling, is anchored to discrete structures within the cell via regulatory subunit interaction with A kinase anchoring proteins (AKAPs) (3Rubin C.S. Biochim. Biophys. Acta. 1994; 1224: 467-479PubMed Google Scholar, 4Colledge M. Scott J.D. Trends Cell Biol. 1999; 9: 216-221Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar). Several different AKAPs that function as scaffold proteins have been characterized. For instance, AKAP79 is part of a multicomplex, which, in addition to the PKA regulatory subunit RII, includes protein kinase C and the phosphatase PP2B/calcineurin (5Coghlan V.M. Perrino B.A. Howard M. Langeberg L.K. Hicks J.B. Gallatin W.M. Scott J.D. Science. 1995; 267: 108-111Crossref PubMed Scopus (524) Google Scholar). Disruption of the PKA interaction with AKAPs abolishes the cAMP-dependent regulation of ion channels (6Rosenmund C. Carr D.W. Bergeson S.E. Nilaver G. Scott J.D. Westbrook G.L. Nature. 1994; 368: 853-856Crossref PubMed Scopus (322) Google Scholar, 7Johnson B.D. Scheuer T. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 11492-11496Crossref PubMed Scopus (157) Google Scholar). PKA regulatory subunits have also been localized in the centrosome in culture cells (8Nigg E.A. Hilz H. Eppenberger H.M. Dutly F. EMBO J. 1985; 4: 2801-2806Crossref PubMed Scopus (197) Google Scholar), and in cells of the central nervous system (9De Camilli P. Moretti M. Donini S.D. Walter U. Lohmann S.M. J. Cell Biol. 1986; 103: 189-203Crossref PubMed Scopus (144) Google Scholar), thus opening the possibility that microenvironments of cAMP signaling may be necessary for intracellular trafficking and organelle movements during cell nucleotide phosphodiesterases, the enzymes that degrade and inactivate cAMP, may play an important role in signaling compartmentalization by controlling cAMP diffusion to the PKA anchored to different the of present in a cell 1995; PubMed Scopus Google Scholar, M. Biol. 1999; PubMed Google Scholar, M. G. C. 1995; PubMed Scopus Google Scholar, M. G.B. PubMed Scopus Google Scholar), are in the particulate of the and have been to different compartments. and have that the PDE4D are particulate or the amino present in the protein G.B. S. G. R. C. J. PubMed Scopus Google Scholar, S. M. T. F. C. M. M. PubMed Scopus Google Scholar, T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), and are located in different subcellular as by cells, and with amino are in the particulate and are localized in a region to structures, as as to the membrane region T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). a third variant the of is is mostly in the and by cAMP is with in these cells T. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of PDE4D in discrete subcellular structures has also been in S. Cell Biophys. PubMed Scopus Google Scholar). These findings open the possibility that the subcellular of PDE4D is and this may be during cAMP signaling. the of subcellular we to proteins that with these PDE4D and to anchor to different Here we the of a novel protein named myomegalin, is a of skeletal and is expressed in cells in cells it is targeted to the Golgi/centrosomal myomegalin in the in heart and skeletal muscle. protein with PDE4D in the cells and these we the and the of myomegalin, a novel protein with the of a splicing of myomegalin detected in rat may functions in and Myomegalin is targeted to the Golgi/centrosomal region in cultured COS-7 and cells and in cells of the whereas in and skeletal it is with the or the that one of the functions of this protein is in cAMP signaling compartmentalization it a of the cAMP signaling to these subcellular is to the was identified for by or 1995; Google and is mostly composed of coiled-coil structures with leucine zipper leucine zipper the amino is to the only leucine zipper found in one variant of in coiled-coil structures is also shared and is a of the and the 1999; Google and is thought to play a role during of the central nervous system and 1995; Google Scholar). A of has been in J. Cell Biol. PubMed Scopus Google Scholar). that the and of the a a splicing variant of the myomegalin is expressed in cells of rat testis and is localized in a Golgi/centrosomal region of and it be it is located in the of the it is that the myomegalin has functions during that with of the be that proteins to the have been These A and and protein G. C. D. J. Cell Sci. Google Scholar, C. G. A. P. H. D. J. Cell Sci. Google Scholar, Cell Biol. PubMed Scopus Google Scholar). to the protein is and myomegalin is to to these function of is present large coiled-coil proteins localized in the have been as a of proteins S. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, C. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar). the and proteins have coiled-coil and a domain the that targeting Myomegalin is to in coiled-coil a domain to the domain be identified the of myomegalin, though the amino of this protein are to it to the of an interaction of PDE4D with the myomegalin was by the of the protein, we have of an interaction of the myomegalin variant with of indicate that the proteins may in a in the cell. addition to the interaction detected with the the variant of myomegalin and PDE4D in a of myomegalin targeted the PDE4D3 to the particulate of COS-7 myomegalin and PDE4D were in cultured cells as as in and skeletal of PDE4D that a of interaction with myomegalin is in a domain that to the amino of the region domain is in the of opening the possibility that may with domain of PDE4D of a region of α-helical with of the of myomegalin also α-helical domains that may the interaction with a the we have that this PDE4D interacts with myomegalin, is also involved in with the regulatory domain and that it functions as an domain that the activity of the J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). it is the interaction and the to myomegalin are or the is it the of myomegalin the activity of the have that of PDE4D3 the interaction of this domain with the amino J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google it is that the of also the of the PDE4D to with studies are to this is that the interaction of PDE4D with myomegalin, and with the may be a and that of this protein may during signaling. have been that PDE4D3 may activation of the protein kinase pathway H. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google of coiled-coil it is that myomegalin with or interacts with of a leucine zipper is also to is with this addition to a proteins may be with a domain to the domain involved in a found in and an domain that an were the of these domains that myomegalin is present in a with proteins, may be involved in or with interaction with structures. the possibility that myomegalin may play a role in the different of the is expressed in skeletal and an important function in with a myomegalin a was in the region or in the be PDE4D and myomegalin are in the or are with the Several transduction proteins have been localized in the region of the adenylyl and the regulatory subunit of PKA T. J. Biol. Full Text Full Text PDF PubMed Scopus Google J. M. J. Cell Biol. PubMed Scopus Google Scholar). it is that myomegalin PDE4D to a in the cAMP signaling in colocalization of PDE4D and myomegalin in Golgi/centrosomal structures to a role of cyclic nucleotide signaling in the function of these of a to the may have an important function in controlling cAMP diffusion to these PKA regulatory and anchoring have also been localized in the and in the centrosome (8Nigg E.A. Hilz H. Eppenberger H.M. Dutly F. EMBO J. 1985; 4: 2801-2806Crossref PubMed Scopus (197) Google Scholar, Camilli P. Moretti M. Donini S.D. Walter U. Lohmann S.M. J. Cell Biol. 1986; 103: 189-203Crossref PubMed Scopus (144) Google Scholar, G. Lohmann S.M. M. Cell PubMed Scopus Google G. M. T. S. EMBO J. 1999; PubMed Scopus Google Scholar). findings that PDE4D in these to the of activation of and the in these role of cAMP signaling in centrosome function and in in the is though is that cAMP as as T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. A. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). is by cAMP J. Cell Biol. PubMed Scopus Google Scholar), and cyclic have been in the of movements Biol. Cell. PubMed Scopus Google Scholar). it is that of a in these via myomegalin interaction may be involved in the of organelle movements or With these we the and the of myomegalin, a novel protein with the of a splicing of myomegalin detected in rat may functions in and Myomegalin is targeted to the Golgi/centrosomal region in cultured COS-7 and cells and in cells of the whereas in and skeletal it is with the or the that one of the functions of this protein is in cAMP signaling compartmentalization it a of the cAMP signaling to these subcellular structures. Myomegalin is to the was identified for by or 1995; Google and is mostly composed of coiled-coil structures with leucine zipper leucine zipper the amino is to the only leucine zipper found in one variant of in coiled-coil structures is also shared and is a of the and the 1999; Google and is thought to play a role during of the central nervous system and 1995; Google Scholar). A of has been in J. Cell Biol. PubMed Scopus Google Scholar). that the and of the a a splicing variant of the myomegalin is expressed in cells of rat testis and is localized in a Golgi/centrosomal region of and it be it is located in the of the it is that the myomegalin has functions during that with of the be that proteins to the have been These A and and protein G. C. D. J. Cell Sci. Google Scholar, C. G. A. P. H. D. J. Cell Sci. Google Scholar, Cell Biol. PubMed Scopus Google Scholar). to the protein is and myomegalin is to to these function of is present large coiled-coil proteins localized in the have been as a of proteins S. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, C. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar). the and proteins have coiled-coil and a domain the that targeting Myomegalin is to in coiled-coil a domain to the domain be identified the of myomegalin, though the amino of this protein are to it to the structures. of an interaction of PDE4D with the myomegalin was by the of the protein, we have of an interaction of the myomegalin variant with of indicate that the proteins may in a in the cell. addition to the interaction detected with the the variant of myomegalin and PDE4D in a of myomegalin targeted the PDE4D3 to the particulate of COS-7 myomegalin and PDE4D were in cultured cells as as in and skeletal of PDE4D that a of interaction with myomegalin is in a domain that to the amino of the region domain is in the of opening the possibility that may with domain of PDE4D of a region of α-helical with of the of myomegalin also α-helical domains that may the interaction with a the we have that this PDE4D interacts with myomegalin, is also involved in with the regulatory domain and that it functions as an domain that the activity of the J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). it is the interaction and the to myomegalin are or the is it the of myomegalin the activity of the have that of PDE4D3 the interaction of this domain with the amino J. G. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google it is that the of also the of the PDE4D to with studies are to this is that the interaction of PDE4D with myomegalin, and with the may be a and that of this protein may during signaling. have been that PDE4D3 may activation of the protein kinase pathway H. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). of coiled-coil it is that myomegalin with or interacts with of a leucine zipper is also to is with this addition to a proteins may be with a domain to the domain involved in a found in and an domain that an were the of these domains that myomegalin is present in a with proteins, may be involved in or with interaction with structures. the possibility that myomegalin may play a role in the different of the Myomegalin is expressed in skeletal and an important function in with a myomegalin a was in the region or in the be PDE4D and myomegalin are in the or are with the Several transduction proteins have been localized in the region of the adenylyl and the regulatory subunit of PKA T. J. Biol. Full Text Full Text PDF PubMed Scopus Google J. M. J. Cell Biol. PubMed Scopus Google Scholar). it is that myomegalin PDE4D to a in the cAMP signaling in colocalization of PDE4D and myomegalin in Golgi/centrosomal structures to a role of cyclic nucleotide signaling in the function of these of a to the may have an important function in controlling cAMP diffusion to these PKA regulatory and anchoring have also been localized in the and in the centrosome (8Nigg E.A. Hilz H. Eppenberger H.M. Dutly F. EMBO J. 1985; 4: 2801-2806Crossref PubMed Scopus (197) Google Scholar, Camilli P. Moretti M. Donini S.D. Walter U. Lohmann S.M. J. Cell Biol. 1986; 103: 189-203Crossref PubMed Scopus (144) Google Scholar, G. Lohmann S.M. M. Cell PubMed Scopus Google G. M. T. S. EMBO J. 1999; PubMed Scopus Google Scholar). findings that PDE4D in these to the of activation of and the in these role of cAMP signaling in centrosome function and in in the is though is that cAMP as as T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. A. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). is by cAMP J. Cell Biol. PubMed Scopus Google Scholar), and cyclic have been in the of movements Biol. Cell. PubMed Scopus Google Scholar). it is that of a in these via myomegalin interaction may be involved in the of organelle movements or for and for the of the and and for and with these
Verde et al. (Sun,) studied this question.