Histochemistry and Cell Biology

, Volume 132, Issue 2, pp 191–198 | Cite as

Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation

  • Jee In Kim
  • Garbo D. Young
  • Li Jin
  • Avril V. Somlyo
  • Masumi Eto
Original Paper

Abstract

Ca2+ sensitivity of smooth muscle (SM) contraction is determined by CPI-17, an inhibitor protein for myosin light chain phosphatase (MLCP). CPI-17 is highly expressed in mature SM cells, but the expression level varies under pathological conditions. Here, we determined the expression of CPI-17 in embryonic SM tissues and arterial neointimal lesions using immunohistochemistry. As seen in adult animals, the predominant expression of CPI-17 was detected at SM tissues on mouse embryonic sections, whereas MLCP was ubiquitously expressed. Compared with SM α-actin, CPI-17 expression doubled in arterial SM from embryonic day E10 to E14. Like SM α-actin and other SM marker proteins, CPI-17 was expressed in embryonic heart, and the expression was down-regulated at E17. In adult rat, CPI-17 expression level was reduced to 30% in the neointima of injured rat aorta, compared with the SM layers, whereas the expression of MLCP was unchanged in both regions. Unlike other SM proteins, CPI-17 was detected at non-SM organs in the mouse embryo, such as embryonic neurons and epithelium. Thus, CPI-17 expression is reversibly controlled in response to the phenotype transition of SM cells that restricts the signal to differentiated SM cells and particular cell types.

Keywords

Smooth muscle contraction Smooth muscle development Vascular biology Vascular injury CPI-17 Myosin light chain phosphatase Myocardin PKC ROCK 

Supplementary material

418_2009_604_MOESM1_ESM.doc (388 kb)
Supplementary Fig. 1 (DOC 388 kb)

References

  1. Aikawa M, Sivam PN, Kuro-o M, Kimura K, Nakahara K, Takewaki S, Ueda M, Yamaguchi H, Yazaki Y, Periasamy M (1993) Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. Circ Res 73:1000–1012PubMedGoogle Scholar
  2. Chang S, Hypolite JA, DiSanto ME, Changolkar A, Wein AJ, Chacko S (2006) Increased basal phosphorylation of detrusor smooth muscle myosin in alloxan-induced diabetic rabbit is mediated by upregulation of Rho-kinase beta and CPI-17. Am J Physiol Renal Physiol 290:F650–F656PubMedCrossRefGoogle Scholar
  3. Dakshinamurti S, Mellow L, Stephens NL (2005) Regulation of pulmonary arterial myosin phosphatase activity in neonatal circulatory transition and in hypoxic pulmonary hypertension: a role for CPI-17. Pediatr Pulmonol 40:398–407PubMedCrossRefGoogle Scholar
  4. Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T (2007) Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. Circ Res 100:121–129PubMedCrossRefGoogle Scholar
  5. Eto M, Kitazawa T, Brautigan DL (2004) Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of protein phosphatase-1 by regulatory subunits. Proc Natl Acad Sci USA 101:8888–8893PubMedCrossRefGoogle Scholar
  6. Eto M, Senba S, Morita F, Yazawa M (1997) Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle. FEBS Lett 410:356–360Google Scholar
  7. Eto M, Bock R, Brautigan DL, Linden DJ (2002) Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor. Neuron 36:1145–1158PubMedCrossRefGoogle Scholar
  8. Eto M, Ohmori T, Suzuki M, Furuya K, Morita F (1995) A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem 118:1104–1107PubMedGoogle Scholar
  9. Etter EF, Eto M, Wardle RL, Brautigan DL, Murphy RA (2001) Activation of myosin light chain phosphatase in intact arterial smooth muscle during nitric oxide-induced relaxation. J Biol Chem 276:34681–34685PubMedCrossRefGoogle Scholar
  10. Hartshorne DJ, Ito M, Erdodi F (2004) Role of protein phosphatase type 1 in contractile functions: myosin phosphatase. J Biol Chem 279:37211–37214PubMedCrossRefGoogle Scholar
  11. Jin H, Sperka T, Herrlich P, Morrison H (2006) Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase. Nature 442:576–579PubMedCrossRefGoogle Scholar
  12. Jin L, Kern MJ, Otey CA, Wamhoff BR, Somlyo AV (2007) Angiotensin II, focal adhesion kinase, and PRX1 enhance smooth muscle expression of lipoma preferred partner and its newly identified binding partner palladin to promote cell migration. Circ Res 100:817–825PubMedCrossRefGoogle Scholar
  13. Kamm KE, Stull JT (2001) Dedicated myosin light chain kinases with diverse cellular functions. J Biol Chem 276:4527–4530PubMedCrossRefGoogle Scholar
  14. Keller BB, MacLennan MJ, Tinney JP, Yoshigi M (1996) In vivo assessment of embryonic cardiovascular dimensions and function in day-10.5 to -14.5 mouse embryos. Circ Res 79:247–255PubMedGoogle Scholar
  15. Kitazawa T, Eto M, Woodsome TP, Brautigan DL (2000) Agonists trigger G protein-mediated activation of CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J Biol Chem 275:9897–9900Google Scholar
  16. Kitazawa T, Polzin AN, Eto M (2004) CPI-17-deficient smooth muscle of chicken. J Physiol 557:515–528PubMedCrossRefGoogle Scholar
  17. Ohama T, Hori M, Sato K, Ozaki H, Karaki H (2003) Chronic treatment with interleukin-1beta attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle. J Biol Chem 278:48794–48804PubMedCrossRefGoogle Scholar
  18. Okubo S, Ito M, Takashiba Y, Ichikawa K, Miyahara M, Shimizu H, Konishi T, Shima H, Nagao M, Hartshorne DJ et al (1994) A regulatory subunit of smooth muscle myosin bound phosphatase. Biochem Biophys Res Commun 200:429–434PubMedCrossRefGoogle Scholar
  19. Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84:767–801PubMedCrossRefGoogle Scholar
  20. Ruzicka DL, Schwartz RJ (1988) Sequential activation of alpha-actin genes during avian cardiogenesis: vascular smooth muscle alpha-actin gene transcripts mark the onset of cardiomyocyte differentiation. J Cell Biol 107:2575–2586PubMedCrossRefGoogle Scholar
  21. Sakai H, Chiba Y, Hirano T, Misawa M (2005) Possible involvement of CPI-17 in augmented bronchial smooth muscle contraction in antigen-induced airway hyper-responsive rats. Mol Pharmacol 68:145–151PubMedGoogle Scholar
  22. Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83:1325–1358PubMedGoogle Scholar
  23. Wang D, Olson EN (2004) Control of smooth muscle development by the myocardin family of transcriptional coactivators. Curr Opin Genet Dev 14:558–566PubMedCrossRefGoogle Scholar
  24. Woodsome TP, Eto M, Everett A, Brautigan DL, Kitazawa T (2001) Expression of CPI-17 and myosin phosphatase correlates with Ca2+ sensitivity of protein kinase C-induced contraction in rabbit smooth muscle. J Physiol 535:553–564PubMedCrossRefGoogle Scholar
  25. Wu Y, Erdodi F, Muranyi A, Nullmeyer KD, Lynch RM, Hartshorne DJ (2003) Myosin phosphatase and myosin phosphorylation in differentiating C2C12 cells. J Muscle Res Cell Motil 24:499–511PubMedCrossRefGoogle Scholar
  26. Yin F, Hoggatt AM, Zhou J, Herring BP (2006) 130-kDa smooth muscle myosin light chain kinase is transcribed from a CArG-dependent, internal promoter within the mouse mylk gene. Am J Physiol Cell Physiol 290:C1599–C1609PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jee In Kim
    • 1
  • Garbo D. Young
    • 1
  • Li Jin
    • 2
  • Avril V. Somlyo
    • 2
  • Masumi Eto
    • 1
    • 3
  1. 1.Department of Molecular Physiology and BiophysicsThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of Molecular Physiology and Biological PhysicsThe University of VirginiaCharlottesvilleUSA
  3. 3.Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA

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