PI3KC2β inactivation stabilizes VE-cadherin junctions and preserves vascular integrity

被引：13

作者：

Anquetil, Typhaine ^{[1
,2
]}

Solinhac, Romain ^{[1
,2
]}

Jaffre, Aude ^{[1
,2
]}

Chicanne, Gaetan ^{[1
,2
]}

Viaud, Julien ^{[1
,2
]}

Darcourt, Jean ^{[1
,2
]}

Orset, Cyrille ^{[3
,4
]}

Geuss, Eva ^{[5
]}

Kleinschnitz, Christoph ^{[6
]}

Vanhaesebroeck, Bart ^{[7
]}

Vivien, Denis ^{[3
,4
,8
]}

Hnia, Karim ^{[1
,2
]}

Larrue, Vincent ^{[1
,2
,9
]}

Payrastre, Bernard ^{[1
,2
,10
]}

Gratacap, Marie-Pierre ^{[1
,2
]}

机构：

[1] INSERM, UMR S U1297, Toulouse, France

[2] Univ Toulouse III, Inst Cardiovasc & Metab Dis I2MC, CHU Rangueil, Toulouse, France

[3] INSERM, UMR S U1237, Caen, France

[4] Caen Normandie Univ, Physiopathol & Imaging Neurol Disorders PhIND, GIP Cyceron, Caen, France

[5] Univ Wurzburg, Dept Neurol, Wurzburg, Germany

[6] Essen Univ Hosp, Dept Neurol, Essen, Germany

[7] UCL, UCL Canc Inst, Cell Signaling, London, England

[8] Caen Univ Hosp, Dept Clin Res, CHU Caen, Caen, France

[9] Univ Hosp Toulouse, Dept Neurol, Toulouse, France

[10] CHU Toulouse, Lab Hematol, Toulouse, France

来源：

EMBO REPORTS | 2021年 / 22卷 / 06期

关键词：

endosomal trafficking; endothelial hyperpermeability; phosphoinositide 3‐ kinase C2β vascular biology; vascular endothelial‐ cadherin; PHOSPHOINOSITIDE 3-KINASE C2-BETA; SENSITIVE MOLECULAR MRI; MODEL; STROKE; PI3K; ANGIOGENESIS; PERMEABILITY; ACTIVATION;

D O I：

10.15252/embr.202051299

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Endothelium protection is critical, because of the impact of vascular leakage and edema on pathological conditions such as brain ischemia. Whereas deficiency of class II phosphoinositide 3-kinase alpha (PI3KC2 alpha) results in an increase in vascular permeability, we uncover a crucial role of the beta isoform (PI3KC2 beta) in the loss of endothelial barrier integrity following injury. Here, we studied the role of PI3KC2 beta in endothelial permeability and endosomal trafficking in vitro and in vivo in ischemic stroke. Mice with inactive PI3KC2 beta showed protection against vascular permeability, edema, cerebral infarction, and deleterious inflammatory response. Loss of PI3KC2 beta in human cerebral microvascular endothelial cells stabilized homotypic cell-cell junctions by increasing Rab11-dependent VE-cadherin recycling. These results identify PI3KC2 beta as a potential new therapeutic target to prevent aggravating lesions following ischemic stroke.

引用

页数：18

共 42 条

[1] HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE [J].

ADES, EW ;

CANDAL, FJ ;

SWERLICK, RA ;

GEORGE, VG ;

SUMMERS, S ;

BOSSE, DC ;

LAWLEY, TJ .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) :683-690

[2] Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity [J].

Alliouachene, Samira ;

Bilanges, Benoit ;

Chicanne, Gaetan ;

Anderson, Karen E. ;

Pearce, Wayne ;

Ali, Khaled ;

Valet, Colin ;

Posor, York ;

Low, Pei Ching ;

Chaussade, Claire ;

Scudamore, Cheryl L. ;

Salamon, Rachel S. ;

Backer, Jonathan M. ;

Stephens, Len ;

Hawkins, Phill T. ;

Payrastre, Bernard ;

Vanhaesebroeck, Bart .

CELL REPORTS, 2015, 13 (09) :1881-1894

[3] RAT MIDDLE CEREBRAL-ARTERY OCCLUSION - EVALUATION OF THE MODEL AND DEVELOPMENT OF A NEUROLOGIC EXAMINATION [J].

BEDERSON, JB ;

PITTS, LH ;

TSUJI, M ;

NISHIMURA, MC ;

DAVIS, RL ;

BARTKOWSKI, H .

STROKE, 1986, 17 (03) :472-476

[4] PI3K isoforms in cell signalling and vesicle trafficking [J].

Bilanges, Benoit ;

Posor, York ;

Vanhaesebroeck, Bart .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2019, 20 (09) :515-534

[5]

Braeuninger S, 2012, METHODS MOL BIOL, V788, P29, DOI 10.1007/978-1-61779-307-3_3

[6] Rab11 activity and PtdIns(3)P turnover removes recycling cargo from endosomes [J].

Campa, Carlo Cosimo ;

Margaria, Jean Piero ;

Derle, Abhishek ;

Del Giudice, Marco ;

De Santis, Maria Chiara ;

Gozzelino, Luca ;

Copperi, Francesca ;

Bosia, Carla ;

Hirsch, Emilio .

NATURE CHEMICAL BIOLOGY, 2018, 14 (08) :801-+

[7] Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro [J].

Chaitanya, Ganta V. ;

Cromer, Walter E. ;

Wells, Shannon R. ;

Jennings, Merilyn H. ;

Couraud, P. Olivier ;

Romero, Ignacio A. ;

Weksler, Babette ;

Erdreich-Epstein, Anat ;

Mathis, J. Michael ;

Minagar, Alireza ;

Alexander, J. Steven .

JOURNAL OF NEUROINFLAMMATION, 2011, 8

[8] A novel mass assay to quantify the bioactive lipid PtdIns3P in various biological samples [J].

Chicanne, Gaetan ;

Severin, Sonia ;

Boscheron, Cecile ;

Terrisse, Anne-Dominique ;

Gratacap, Marie-Pierre ;

Gaits-Iacovoni, Frederique ;

Tronchere, Helene ;

Payrastre, Bernard .

BIOCHEMICAL JOURNAL, 2012, 447 :17-23

[9] Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression [J].

Chikh, Anissa ;

Ferro, Riccardo ;

Abbott, Jonathan J. ;

Pineiro, Roberto ;

Buus, Richard ;

Iezzi, Manuela ;

Ricci, Francesca ;

Bergamaschi, Daniele ;

Ostano, Paola ;

Chiorino, Giovanna ;

Lattanzio, Rossano ;

Broggini, Massimo ;

Piantelli, Mauro ;

Maffucci, Tania ;

Falasca, Marco .

ONCOTARGET, 2016, 7 (14) :18325-18345

[10] Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier [J].

Daniels, Brian P. ;

Cruz-Orengo, Lillian ;

Pasieka, Tracy Jo ;

Couraud, Pierre-Olivier ;

Romero, Ignacio A. ;

Weksler, Babette ;

Cooper, John A. ;

Doering, Tamara L. ;

Klein, Robyn S. .

JOURNAL OF NEUROSCIENCE METHODS, 2013, 212 (01) :173-179

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