دورية أكاديمية
أعرض في EDS

Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.

التفاصيل البيبلوغرافية
العنوان: Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.
المؤلفون: Sarker M; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Goliaei A; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Golesi F; Aix Marseille University, INSERM, INRA, Marseille, France., Poggi M; Aix Marseille University, INSERM, INRA, Marseille, France., Cook AA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Khan MAI; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Temple BR; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; RL Juliano Structural Bioinformatics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Stefanini L; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Canault M; Aix Marseille University, INSERM, INRA, Marseille, France., Bergmeier W; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Campbell SL; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
المصدر: Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2020 Mar; Vol. 18 (3), pp. 693-705. Date of Electronic Publication: 2019 Dec 30.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE
أسماء مطبوعة: Publication: 2023- : [New York] : Elsevier
Original Publication: Oxford : Blackwell Pub.
مواضيع طبية MeSH: GTP Phosphohydrolase Activators* , Phosphatidylinositols*, GTP Phosphohydrolases ; Guanine Nucleotide Exchange Factors ; Signal Transduction
مستخلص: Background: The small GTPase Rap1 and its guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), are critical for platelet function and hemostatic plug formation. CDGI function is regulated by a calcium binding EF hand regulatory domain and an atypical C1 domain with unknown function.
Objective: Here, we investigated whether the C1 domain controls CDGI subcellular localization, both in vitro and in vivo.
Methods: CDGI interaction with phosphoinositides was studied by lipid co-sedimentation assays and molecular dynamics simulations. Cellular localization of CDGI was studied in heterologous cells by immunofluorescence and subcellular fractionation assays.
Results: Lipid co-sedimentation studies demonstrated that the CDGI C1 domain associates with membranes through exclusive recognition of phosphoinositides, phosphatidylinositol (4,5)-biphosphate (PIP2) and phosphatidylinositol (3,4,5)-triphosphate (PIP3). Molecular dynamics simulations identified a phospholipid recognition motif consisting of residues exclusive to the CDGI C1 domain. Mutation of those residues abolished co-sedimentation of the C1 domain with lipid vesicles and impaired membrane localization of CDGI in heterologous cells.
Conclusion: Our studies identify a novel interaction between an atypical C1 domain and phosphatidylinositol (4,5)-biphosphate and phosphatidylinositol (3,4,5)-triphosphate in cellular membranes, which is critical for Rap1 signaling in health and disease.
(© 2019 International Society on Thrombosis and Haemostasis.)
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معلومات مُعتمدة: R01 GM115597 United States GM NIGMS NIH HHS; P01 CA203657 United States CA NCI NIH HHS; 1R35 HL144976-01 United States NH NIH HHS; R35 HL144976 United States HL NHLBI NIH HHS; P30 CA016086 United States CA NCI NIH HHS; R35 GM134962 United States GM NIGMS NIH HHS; PO1 CA203657 United States NH NIH HHS; 1R01GM115597 United States NH NIH HHS; P30 CA016086 United States NH NIH HHS
فهرسة مساهمة: Keywords: C1 domain; CalDAG-GEF; membrane; platelet; thrombosis
المشرفين على المادة: 0 (GTP Phosphohydrolase Activators)
0 (Guanine Nucleotide Exchange Factors)
0 (Phosphatidylinositols)
EC 3.6.1.- (GTP Phosphohydrolases)
تواريخ الأحداث: Date Created: 20191124 Date Completed: 20210514 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7050387
DOI: 10.1111/jth.14687
PMID: 31758832
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-7836
DOI:10.1111/jth.14687