Abstract
Background: Endothelial cells provide a barrier between blood and tissues, which is regulated to allow molecules
and cells in out of tissues. Patients with cerebral cavernous malformations (CCM) have dilated leaky blood vessels,
especially in the central nervous system. A subset of these patients has loss-of-function mutations in CCM3. CCM3
is part of the STRIPAK protein complex that includes the little-characterized proteins FAM40A and FAM40B.
Results: We show here that FAM40A and FAM40B can interact with CCM3. Knockdown of CCM3, FAM40A or FAM40B
in endothelial cells by RNAi causes an increase in stress fibers and a reduction in loop formation in an in vitro angiogenesis
assay, which can be reverted by inhibiting the Rho-regulated ROCK kinases. FAM40B depletion also increases endothelial
permeability.
Conclusions: These results demonstrate the importance of the FAM40 proteins for endothelial cell physiology, and suggest
that they act as part of the CCM3-containing STRIPAK complex.
and cells in out of tissues. Patients with cerebral cavernous malformations (CCM) have dilated leaky blood vessels,
especially in the central nervous system. A subset of these patients has loss-of-function mutations in CCM3. CCM3
is part of the STRIPAK protein complex that includes the little-characterized proteins FAM40A and FAM40B.
Results: We show here that FAM40A and FAM40B can interact with CCM3. Knockdown of CCM3, FAM40A or FAM40B
in endothelial cells by RNAi causes an increase in stress fibers and a reduction in loop formation in an in vitro angiogenesis
assay, which can be reverted by inhibiting the Rho-regulated ROCK kinases. FAM40B depletion also increases endothelial
permeability.
Conclusions: These results demonstrate the importance of the FAM40 proteins for endothelial cell physiology, and suggest
that they act as part of the CCM3-containing STRIPAK complex.
| Original language | English |
|---|---|
| Number of pages | 13 |
| Journal | BMC Cell Biology |
| Volume | 19 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - 3 Dec 2018 |
Keywords
- Cerebral cavernous malformations
- STRIPAK complex
- Rho/ROCK
- Adherens junctions
- Actin cytoskeleton
- Endothelial cells