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Dynamic Regulation of the Cerebral Cavernous Malformation Pathway Controls Vascular Stability and Growth
- Source :
- Developmental Cell. (2):342-355
- Publisher :
- Elsevier Inc.
-
Abstract
- SummaryCardiovascular growth must balance stabilizing signals required to maintain endothelial connections and network integrity with destabilizing signals that enable individual endothelial cells to migrate and proliferate. The cerebral cavernous malformation (CCM) signaling pathway utilizes the adaptor protein CCM2 to strengthen endothelial cell junctions and stabilize vessels. Here we identify a CCM2 paralog, CCM2L, that is expressed selectively in endothelial cells during periods of active cardiovascular growth. CCM2L competitively blocks CCM2-mediated stabilizing signals biochemically, in cultured endothelial cells, and in developing mice. Loss of CCM2L reduces endocardial growth factor expression and impairs tumor growth and wound healing. Our studies identify CCM2L as a molecular mechanism by which endothelial cells coordinately regulate vessel stability and growth during cardiovascular development, as well as postnatal vessel growth.
- Subjects :
- medicine.medical_treatment
Molecular Sequence Data
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Mice
Vasculogenesis
Proto-Oncogene Proteins
medicine
Animals
Amino Acid Sequence
KRIT1 Protein
Molecular Biology
Central Nervous System Vascular Malformations
Mice, Knockout
Neovascularization, Pathologic
Sequence Homology, Amino Acid
Growth factor
Microfilament Proteins
Gene Expression Regulation, Developmental
Cell Biology
Embryo, Mammalian
Cell biology
Endothelial stem cell
Vascular endothelial growth factor B
Vascular endothelial growth factor A
Intercellular Junctions
Vascular endothelial growth factor C
Signal transduction
Wound healing
Microtubule-Associated Proteins
Sequence Alignment
Protein Binding
Signal Transduction
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15345807
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental Cell
- Accession number :
- edsair.doi.dedup.....2b54a782558e64b1509ee3276b294dea
- Full Text :
- https://doi.org/10.1016/j.devcel.2012.06.004