Myomegalin Explained

Myomegalin, also known as phosphodiesterase 4D-interacting protein or cardiomyopathy-associated protein 2, is a protein that in humans is encoded by the PDE4DIP gene.^{[1] [2] [3]} It has roles in the formation of microtubules from the centrosome.^[4] Its name derives from the fact that it is highly expressed in units of tubular myofibrils known as sarcomeres and is a large protein, at 2,324 amino acids. It was first characterised in 2000.

Structure and function

Myomegalin is mostly composed of alpha-helix and coiled-coil structures and has domains shared with microtubule-associated proteins.^[5] It has several isoforms, at least two of which have been characterised, CM-MMG and EB-MMG.

Myomegalin is necessary for the sufficient growth of microtubules from the centrosomes. The CM-MMG isoform binds at the centrosome with γ-tubulin in an AKAP9-dependent manner and on the near side of the Golgi apparatus, while the EB-MMG isoform binds with MAPRE1 at the Golgi apparatus and increases MAPRE1's effects on microtubule growth.

Myomegalin, specifically the CM-MMG isoform, is a paralogue of CDK5RAP2.^{[6] [7]} Myomegalin depletion in cells does not lead to decreases in γ-tubulin or CDK5RAP2, unlike CDK5RAP2 depletion, and does not appear to affect mitosis through various spindle anchoring and orientation defects, unlike CDK5RAP2. This indicates that CDK5RAP2 can somewhat serve to compensate for the absence of myomegalin. However, myomegalin-depleted cells have slower migration, since microtubules are crucial for cell motility.

Orthologues of myomegalin are seen in vertebrates as far back as bony fish, around 450 million years ago. In mammals, around 200 million years ago, myomegalin gained an Olduvai domain. Olduvai domains have so far only elsewhere been found in NBPF genes in placental mammals, many of which are adjacent to myomegalin on chromosome 1, so it is believed that these genes originated from a duplication of myomegalin.^[8] Increased NPBF Olduvai domain duplications in humans have been implicated in human brain size evolution.^[9]

Interactions

Myomegalin (PDE4DIP) has been shown to interact with PDE4D.

History

The protein was discovered in 2000 and was so named because it was highly expressed in rat heart muscle sarcomeres (units of tubular myofibrils) and is a large protein, at 2,324 amino acids.

See also

• 1q21.1 deletion syndrome
• 1q21.1 duplication syndrome

Further reading

• Soejima H, Kawamoto S, Akai J, Miyoshi O, Arai Y, Morohka T, Matsuo S, Niikawa N, Kimura A, Okubo K, Mukai T . 6 . Isolation of novel heart-specific genes using the BodyMap database . Genomics . 74 . 1 . 115–20 . May 2001 . 11374908 . 10.1006/geno.2001.6527 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . 6 . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . 6 . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Shimada H, Kuboshima M, Shiratori T, Nabeya Y, Takeuchi A, Takagi H, Nomura F, Takiguchi M, Ochiai T, Hiwasa T . 6 . Serum anti-myomegalin antibodies in patients with esophageal squamous cell carcinoma . International Journal of Oncology . 30 . 1 . 97–103 . January 2007 . 17143517 . 10.3892/ijo.30.1.97 . free .

Notes and References

1. Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O . 6 . Characterization of cDNA clones in size-fractionated cDNA libraries from human brain . DNA Research . 4 . 5 . 345–9 . October 1997 . 9455484 . 10.1093/dnares/4.5.345 . free .
2. Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M . 6 . Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase . The Journal of Biological Chemistry . 276 . 14 . 11189–98 . April 2001 . 11134006 . 10.1074/jbc.M006546200 . free . 11573/1681344 . free .
3. Web site: Entrez Gene: PDE4DIP phosphodiesterase 4D interacting protein (myomegalin).
4. Roubin R, Acquaviva C, Chevrier V, Sedjaï F, Zyss D, Birnbaum D, Rosnet O . Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules . Biology Open . 2 . 2 . 238–50 . February 2013 . 23430395 . 3575658 . 10.1242/bio.20123392 .
5. Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M . 6 . Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase . The Journal of Biological Chemistry . 276 . 14 . 11189–98 . April 2001 . 11134006 . 10.1074/jbc.M006546200 . free . 11573/1681344 . free .
6. Dumas L, Kim YH, Karimpour-Fard A, Cox M, Hopkins J, Pollack JR, Sikela JM . Gene copy number variation spanning 60 million years of human and primate evolution . Genome Research . 17 . 9 . 1266–77 . September 2007 . 17666543 . 1950895 . 10.1101/gr.6557307 .
7. O'Bleness MS, Dickens CM, Dumas LJ, Kehrer-Sawatzki H, Wyckoff GJ, Sikela JM . Evolutionary history and genome organization of DUF1220 protein domains . G3 . 2 . 9 . 977–86 . September 2012 . 22973535 . 3429928 . 10.1534/g3.112.003061 .
8. O'Bleness MS, Dickens CM, Dumas LJ, Kehrer-Sawatzki H, Wyckoff GJ, Sikela JM . Evolutionary history and genome organization of DUF1220 protein domains . G3 . 2 . 9 . 977–86 . September 2012 . 22973535 . 3429928 . 10.1534/g3.112.003061 .
9. Sikela JM, van Roy F . Changing the name of the NBPF/DUF1220 domain to the Olduvai domain . F1000Research . 6 . 2185 . 2185 . 2018 . 29399325 . 5773923 . 10.12688/f1000research.13586.1 . free .