The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs
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 pat...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
|
| Series: | BMC Cell Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12860-018-0175-y |
| _version_ | 1818943012195008512 |
|---|---|
| author | Narendra Suryavanshi Joanna Furmston Anne J. Ridley |
| author_facet | Narendra Suryavanshi Joanna Furmston Anne J. Ridley |
| author_sort | Narendra Suryavanshi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:20:33Z |
| format | Article |
| id | doaj.art-8c97f250e71a424e884d90ae35cf8aa1 |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-12-20T07:20:33Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-8c97f250e71a424e884d90ae35cf8aa12022-12-21T19:48:41ZengBMCBMC Cell Biology1471-21212018-12-0119111310.1186/s12860-018-0175-yThe STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKsNarendra Suryavanshi0Joanna Furmston1Anne J. Ridley2Randall Centre for Cell and Molecular Biophysics, King’s College London, New Hunt’s House, Guy’s CampusRandall Centre for Cell and Molecular Biophysics, King’s College London, New Hunt’s House, Guy’s CampusRandall Centre for Cell and Molecular Biophysics, King’s College London, New Hunt’s House, Guy’s CampusAbstract 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.http://link.springer.com/article/10.1186/s12860-018-0175-yCerebral cavernous malformationsEndothelial cellsActin cytoskeletonAdherens junctionsRho/ROCKSTRIPAK complex |
| spellingShingle | Narendra Suryavanshi Joanna Furmston Anne J. Ridley The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs BMC Cell Biology Cerebral cavernous malformations Endothelial cells Actin cytoskeleton Adherens junctions Rho/ROCK STRIPAK complex |
| title | The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs |
| title_full | The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs |
| title_fullStr | The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs |
| title_full_unstemmed | The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs |
| title_short | The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs |
| title_sort | stripak complex components fam40a and fam40b regulate endothelial cell contractility via rocks |
| topic | Cerebral cavernous malformations Endothelial cells Actin cytoskeleton Adherens junctions Rho/ROCK STRIPAK complex |
| url | http://link.springer.com/article/10.1186/s12860-018-0175-y |
| work_keys_str_mv | AT narendrasuryavanshi thestripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks AT joannafurmston thestripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks AT annejridley thestripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks AT narendrasuryavanshi stripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks AT joannafurmston stripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks AT annejridley stripakcomplexcomponentsfam40aandfam40bregulateendothelialcellcontractilityviarocks |