Rap1 signaling in endothelial barrier control.
The small G-protein Rap1 plays an important role in the regulation of endothelial barrier function, a process controlled largely by cellâ€"cell adhesions and their connection to the actin cytoskeleton. During the various stages of barrier dynamics, different guanine nucleotide exchange factors (GEFs) control Rap1 activity, indicating that Rap1 integrates multiple input signals. Once activated, Rap1 induces numerous signaling cascades, together responsible for the increased endothelial barrier function. Most notably, Rap1 activation results in the inhibition of Rho to decrease radial stress fibers and the activation of Cdc42 to increase junctional actin. This implies that Rap regulates endothelial barrier function by dual control of cytoskeletal tension. The molecular details of the signaling pathways are becoming to be elucidated.
Molecular Cancer Research and Cancer Genomics Netherlands; University Medical Center Utrecht; Utrecht, The Netherlands.
Willem-Jan
WJ
Pannekoek
Molecular Cancer Research and Cancer Genomics Netherlands; University Medical Center Utrecht; Utrecht, The Netherlands.
Anneke
A
Post
Molecular Cancer Research and Cancer Genomics Netherlands; University Medical Center Utrecht; Utrecht, The Netherlands.
Johannes L
JL
Bos
D008841:Actin Cytoskeleton / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000075927:KRIT1 Protein; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000235:genetics; D022502:Stress Fibers / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; C116122:RAPGEF3 protein, human; C487329:RASIP1 protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
cdc42; cytoskeletal tension; endothelial barrier function; epac1; krit1; radil; rap1; rasip1; rho