caa a22 4500 606175989 CHVBK 20210128100745.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1762-5 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1762-5 Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling [Elektronische Daten] [Agnieszka Płóciennikowska, Aneta Hromada-Judycka, Kinga Borzęcka, Katarzyna Kwiatkowska] Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS), a component of Gram-negative bacteria to induce production of pro-inflammatory mediators aiming at eradication of the bacteria. Dysregulation of the host responses to LPS can lead to a systemic inflammatory condition named sepsis. In a typical scenario, activation of TLR4 is preceded by binding of LPS to CD14 protein anchored in cholesterol- and sphingolipid-rich microdomains of the plasma membrane called rafts. CD14 then transfers the LPS to the TLR4/MD-2 complex which dimerizes and triggers MyD88- and TRIF-dependent production of pro-inflammatory cytokines and type I interferons. The TRIF-dependent signaling is linked with endocytosis of the activated TLR4, which is controlled by CD14. In addition to CD14, other raft proteins like Lyn tyrosine kinase of the Src family, acid sphingomyelinase, CD44, Hsp70, and CD36 participate in the TLR4 signaling triggered by LPS and non-microbial endogenous ligands. In this review, we summarize the current state of the knowledge on the involvement of rafts in TLR4 signaling, with an emphasis on how the raft proteins regulate the TLR4 signaling pathways. CD14-bearing rafts, and possibly CD36-rich rafts, are believed to be preferred sites of the assembly of a multimolecular complex which mediates the endocytosis of activated TLR4. The Author(s), 2014 Lipopolysaccharide nationallicence Toll-like receptor 4 nationallicence Plasma membrane rafts nationallicence CD14 nationallicence Lyn tyrosine kinase nationallicence Acid sphingomyelinase nationallicence CD36 nationallicence Płóciennikowska Agnieszka Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut Hromada-Judycka Aneta Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut Borzęcka Kinga Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut Kwiatkowska Katarzyna Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut Cellular and Molecular Life Sciences Springer Basel 72/3(2015-02-01), 557-581 1420-682X 72:3<557 2015 72 18 https://doi.org/10.1007/s00018-014-1762-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1762-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Płóciennikowska Agnieszka Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut NATIONALLICENCE 700 1- Hromada-Judycka Aneta Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut NATIONALLICENCE 700 1- Borzęcka Kinga Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut NATIONALLICENCE 700 1- Kwiatkowska Katarzyna Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/3(2015-02-01), 557-581 1420-682X 72:3<557 2015 72 18