دورية أكاديمية
CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function.
| العنوان: | CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function. |
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| المؤلفون: | Mao Y; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA., Kleinjan ML; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA., Jilishitz I; Weill Cornell Medicine, New York, NY, USA., Swaminathan B; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA., Obinata H; Education and Research Support Center, Gunma University Graduate School of Medicine, Gunma, Japan., Komarova YA; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA., Bayless KJ; Department of Molecular & Cellular Medicine, Texas A&M System Health Science Center, Bryan, TX, USA., Hla T; Vascular Biology Program, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA, USA., Kitajewski JK; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA. kitaj@uic.edu. |
| المصدر: | Science signaling [Sci Signal] 2021 Apr 20; Vol. 14 (679). Date of Electronic Publication: 2021 Apr 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101465400 Publication Model: Electronic Cited Medium: Internet ISSN: 1937-9145 (Electronic) Linking ISSN: 19450877 NLM ISO Abbreviation: Sci Signal Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Neuropeptides*/metabolism , Sphingosine-1-Phosphate Receptors*/metabolism , rac1 GTP-Binding Protein*/metabolism , rhoA GTP-Binding Protein*/metabolism, Chloride Channels/*metabolism , Mitochondrial Proteins/*metabolism, Animals ; Cell Line ; Cells, Cultured ; Endothelial Cells ; Lysophospholipids ; Mice ; Receptors, Lysosphingolipid/genetics ; Signal Transduction ; Sphingosine |
| مستخلص: | Chloride intracellular channels 1 (CLIC1) and 4 (CLIC4) are expressed in endothelial cells and regulate angiogenic behaviors in vitro, and the expression of Clic4 is important for vascular development and function in mice. Here, we found that CLIC1 and CLIC4 in endothelial cells regulate critical G protein-coupled receptor (GPCR) pathways associated with vascular development and disease. In cultured endothelial cells, we found that CLIC1 and CLIC4 transiently translocated to the plasma membrane in response to sphingosine 1-phosphate (S1P). Both CLIC1 and CLIC4 were essential for mediating S1P-induced activation of the small guanosine triphosphatase (GTPase) Rac1 downstream of S1P receptor 1 (S1PR1). In contrast, only CLIC1 was essential for S1P-induced activation of the small GTPase RhoA downstream of S1PR2 and S1PR3. Neither were required for other S1P-S1PR signaling outputs. Rescue experiments revealed that CLIC1 and CLIC4 were not functionally interchangeable, suggesting distinct and specific functions for CLICs in transducing GPCR signaling. These CLIC-mediated mechanisms were critical for S1P-induced stimulation of the barrier function in endothelial cell monolayers. Our results define CLICs as previously unknown players in the pathways linking GPCRs to small GTPases and vascular endothelial function. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
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| معلومات مُعتمدة: | R01 GM134032 United States GM NIGMS NIH HHS; R01 HL112626 United States HL NHLBI NIH HHS; R01 HL119043 United States HL NHLBI NIH HHS; R35 HL135821 United States HL NHLBI NIH HHS |
| المشرفين على المادة: | 0 (CLIC protein, mouse) 0 (Chloride Channels) 0 (Clic1 protein, mouse) 0 (Lysophospholipids) 0 (Mitochondrial Proteins) 0 (Neuropeptides) 0 (Rac1 protein, mouse) 0 (Receptors, Lysosphingolipid) 0 (Sphingosine-1-Phosphate Receptors) EC 3.6.5.2 (RhoA protein, mouse) EC 3.6.5.2 (rac1 GTP-Binding Protein) EC 3.6.5.2 (rhoA GTP-Binding Protein) NGZ37HRE42 (Sphingosine) |
| تواريخ الأحداث: | Date Created: 20210421 Date Completed: 20220113 Latest Revision: 20220531 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8722429 |
| DOI: | 10.1126/scisignal.abc0425 |
| PMID: | 33879602 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1937-9145 |
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| DOI: | 10.1126/scisignal.abc0425 |