The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases

Nature Medicine

Volumn 15, Issue 2, 2009, Pages 177-184

  Whitehead, Kevin J ^a   Chan, Aubrey C ^a   Navankasattusas, Sutip ^a   Koh, Wonshill ^b   London, Nyall R ^a   Ling, Jing ^a   Mayo, Anne H ^b   Drakos, Stavros G ^a   Marchuk, Douglas A ^c   Davis, George E ^b   Li, Dean Y ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b University of Missouri   (United States)

^c DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; MITOGEN ACTIVATED PROTEIN KINASE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SIMVASTATIN;

ANGIOGENESIS; ANIMAL EXPERIMENT; ARTICLE; BRAIN MALFORMATION; CCM2 GENE; CELL INTERACTION; CONTROLLED STUDY; CYTOSKELETON; EMBRYO; EMBRYO DEATH; ENDOTHELIUM CELL; GENE; GENE DISRUPTION; GENE LOSS; GENOTYPE; HETEROZYGOSITY; HUMAN; HUMAN CELL; MORPHOGENESIS; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; VASCULAR DISEASE; VASCULARIZATION;

ANIMALS; BLOOD VESSELS; CARRIER PROTEINS; HETEROZYGOTE; HUMANS; MICE; RHO GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION;

MUS;

EID: 59649084619     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.1911     Document Type: Article

References (41)

1. Otten, P., Pizzolato, G.P., Rilliet, B. & Berney, J. A propos de 131 cas d'angiomes caverneux (cavernomes) du S.N.C. repérés par l'analyse rétrospective de 24 535 autopsies. Neurochirurgie 35, 82-83 128-131 (1989).
2. Robinson, J.R., Awad, I.A. & Little, J.R. Natural history of the cavernous angioma. J. Neurosurg. 75, 709-714 (1991).
3. Hasegawa, T. et al. Long-term results after stereotactic radiosurgery for patients with cavernous malformations. Neurosurgery 50, 1190-1197 discussion 1197-1198 (2002).
4. Chappell, P.M., Steinberg, G.K. & Marks, M.P. Clinically documented hemorrhage in cerebral arteriovenous malformations: MR characteristics. Radiology 183, 719-724 (1992).
5. Clatterbuck, R.E., Eberhart, C.G., Crain, B.J. & Rigamonti, D. Ultrastructural and immunocytochemical evidence that an incompetent blood-brain barrier is related to the pathophysiology of cavernous malformations. J. Neurol. Neurosurg. Psychiatry 71, 188-192 (2001).
6. Toldo, I., Drigo, P., Mammi, I., Marini, V. & Carollo, C. Vertebral and spinal cavernous angiomas associated with familial cerebral cavernous malformation. Surg. Neurol. published online, doi:10.1016/j.surneu.2007. 07.067 (22 January 2008).
7. Liquori, C.L. et al. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am. J. Hum. Genet. 73, 1459-1464 (2003).
8. Denier, C. et al. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am. J. Hum. Genet. 74, 326-337 (2004).
9. Sahoo, T. et al. Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum. Mol. Genet. 8, 2325-2333 (1999).
10. Laberge-le Couteulx, S. et al. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat. Genet. 23, 189-193 (1999).
11. Bergametti, F. et al. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am. J. Hum. Genet. 76, 42-51 (2005).
12. Uhlik, M.T. et al. Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock. Nat. Cell Biol. 5, 1104-1110 (2003).
13. Petit, N., Blecon, A., Denier, C. & Tournier-Lasserve, E. Patterns of expression of the three cerebral cavernous malformation (CCM) genes during embryonic and postnatal brain development. Gene Expr. Patterns 6, 495-503 (2006).
14. Plummer, N.W. et al. Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations. Mamm. Genome 17, 119-128 (2006).
15. Seker, A. et al. CCM2 expression parallels that of CCM1. Stroke 37, 518-523 (2006).
16. McCarty, J.H. et al. Selective ablation of av integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death. Development 132, 165-176 (2005).
17. Glading, A., Han, J., Stockton, R.A. & Ginsberg, M.H. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J. Cell Biol. 179, 247-254 (2007).
18. Risau, W. Mechanisms of angiogenesis. Nature 386, 671-674 (1997).
19. Su, H., Mills, A.A., Wang, X. & Bradley, A. A targeted X-linked CMV-Cre line. Genesis 32, 187-188 (2002).
20. Kisanuki, Y.Y. et al. Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev. Biol. 230, 230-242 (2001).
21. Sclafani, A.M. et al. Nestin-Cre mediated deletion of Pitx2 in the mouse. Genesis 44, 336-344 (2006).
22. Lepore, J.J. et al. High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22a-Cre transgenic mice. Genesis 41, 179-184 (2005).
23. Kamei, M. et al. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature 442, 453-456 (2006).
24. Bayless, K.J. & Davis, G.E. Microtubule depolymerization rapidly collapses capillary tube networks in vitro and angiogenic vessels in vivo through the small GTPase Rho. J. Biol. Chem. 279, 11686-11695 (2004).
25. Wojciak-Stothard, B., Potempa, S., Eichholtz, T. & Ridley, A.J. Rho and Rac but not Cdc42 regulate endothelial cell permeability. J. Cell Sci. 114, 1343-1355 (2001).
26. Mohr, C., Koch, G., Just, I. & Aktories, K. ADP-ribosylation by Clostridium botulinum C3 exoenzyme increases steady-state GTPase activities of recombinant rhoA and rhoB proteins. FEBS Lett. 297, 95-99 (1992).
27. Hirose, M. et al. Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J. Cell Biol. 141, 1625-1636 (1998).
28. Kyriakis, J.M. & Avruch, J. Sounding the alarm: protein kinase cascades activated by stress and inflammation. J. Biol. Chem. 271, 24313-24316 (1996).
29. Jung, K.H. et al. Cerebral cavernous malformations with dynamic and progressive course: correlation study with vascular endothelial growth factor. Arch. Neurol. 60, 1613-1618 (2003).
30. Larson, J.J., Ball, W.S., Bove, K.E., Crone, K.R. & Tew, J.M.,, Jr. Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J. Neurosurg. 88, 51-56 (1998).
31. Shi, C., Shenkar, R., Batjer, H.H., Check, I.J. & Awad, I.A. Oligoclonal immune response in cerebral cavernous malformations. Laboratory investigation. J. Neurosurg. 107, 1023-1026 (2007).
32. Gault, J., Shenkar, R., Recksiek, P. & Awad, I.A. Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion. Stroke 36, 872-874 (2005).
33. Zeng, L. et al. HMG CoA reductase inhibition modulates VEGF-induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation. FASEB J. 19, 1845-1847 (2005).
34. Park, H.J. et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ. Res. 91, 143-150 (2002).
35. Kranenburg, O., Poland, M., Gebbink, M., Oomen, L. & Moolenaar, W.H. Dissociation of LPA-induced cytoskeletal contraction from stress fiber formation by differential localization of RhoA. J. Cell Sci. 110, 2417-2427 (1997).
36. Collisson, E.A., Carranza, D.C., Chen, I.Y. & Kolodney, M.S. Isoprenylation is necessary for the full invasive potential of RhoA overexpression in human melanoma cells. J. Invest. Dermatol. 119, 1172-1176 (2002).
37. Im, E. & Kazlauskas, A. Src family kinases promote vessel stability by antagonizing the Rho/ROCK pathway. J. Biol. Chem. 282, 29122-29129 (2007).
38. Mavria, G. et al. ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell 9, 33-44 (2006).
39. Whitehead, K.J., Plummer, N.W., Adams, J.A., Marchuk, D.A. & Li, D.Y. Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development 131, 1437-1448 (2004).
40. 1 integrin-dependent pinocytic mechanism involving intracellular vacuole formation and coalescence regulates capillary lumen and tube formation in three-dimensional collagen matrix. Exp. Cell Res. 224, 39-51 (1996).
41. Saunders, W.B. et al. Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J. Cell Biol. 175, 179-191 (2006).