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Mol Biosyst. 2014 Jul;10(7):1881-9. doi: 10.1039/c3mb70199a.

Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis.

Author information

1
David H. Murdock Research Institute, North Carolina Research Campus, Kannapolis, NC 28081, USA.

Abstract

Three genetic mutations were found to cause cerebral cavernous malformation (CCM), a vascular anomaly predisposing affected individuals to hemorrhagic stroke. These CCM proteins function together as a protein complex in the cell. Loss of expression of each CCM gene results in loss of in vitro endothelial tube formation. Label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) was applied to explore the proteomic profile for loss of each CCM gene expression in mouse endothelial stem cells (MEES) compared to mock shRNA and no shRNA control cell-lines. Differentially expressed proteins were identified (p < 0.05). 120 proteins were differentially expressed among the cell-lines. Principal component analysis and cluster analysis show the effects of individual knockdown. In all knockdown cell-lines, altered expression of cytoskeletal proteins is the most common. While all CCM mutations result in similar pathology, different CCM mutations have their own distinct pathogenesis in cell signaling.

PMID:
24770493
PMCID:
PMC4043921
DOI:
10.1039/c3mb70199a
[Indexed for MEDLINE]
Free PMC Article

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