Deciphering the complex three-way interaction between the non-integrin laminin receptor, galectin-3 and Neisseria meningitidis
| Autor: | Necmettin Pirinccioglu, Shaun Morroll, Pierre-Joseph Royer, Nicholas D. Holliday, Jeroen Stoof, Fulwah Yahya Alqahtani, Jafar Mahdavi, Siew Y. Teo, Suzan M. Qarani, Dlawer A. A. Ala'Aldeen, Neil J. Oldfield, Lee M. Wheldon, Matthew Vassey, Karl G. Wooldridge |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Integrins Galectin 3 Molecular Conformation Lactose Ligands Cell membrane Mice Bimolecular fluorescence complementation Chlorocebus aethiops lcsh:QH301-705.5 education.field_of_study Microscopy Confocal COS cells lamr1 biology General Neuroscience Isotype 67 kDa Laminin Receptor Cross-Linking Reagents medicine.anatomical_structure Biochemistry COS Cells Research Article Immunology Population Integrin 37lrp General Biochemistry Genetics and Molecular Biology Receptors Laminin LAMR1 RPSA galectin-3 37LRP 67LR Neisseria meningitidis rpsa neisseria meningitidis galectin-3 medicine Animals Humans education Research Cell Membrane Endothelial Cells Hydrogen Bonding Gene Expression Regulation Microscopy Fluorescence lcsh:Biology (General) Pilin Mutagenesis Site-Directed biology.protein Protein Multimerization 67lr |
| Zdroj: | Open Biology, Vol 4, Iss 10 (2014) Open Biology |
| ISSN: | 2046-2441 |
| Popis: | The non-integrin laminin receptor (LAMR1/RPSA) and galectin-3 (Gal-3) are multi-functional host molecules with roles in diverse pathological processes, particularly of infectious or oncogenic origins. Using bimolecular fluorescence complementation and confocal imaging, we demonstrate that the two proteins homo- and heterodimerize, and that each isotype forms a distinct cell surface population. We present evidence that the 37 kDa form of LAMR1 (37LRP) is the precursor of the previously described 67 kDa laminin receptor (67LR), whereas the heterodimer represents an entity that is distinct from this molecule. Site-directed mutagenesis confirmed that the single cysteine (C 173 ) of Gal-3 or lysine (K 166 ) of LAMR1 are critical for heterodimerization. Recombinant Gal-3, expressed in normally Gal-3-deficient N2a cells, dimerized with endogenous LAMR1 and led to a significantly increased number of internalized bacteria ( Neisseria meningitidis ), confirming the role of Gal-3 in bacterial invasion. Contact-dependent cross-linking determined that, in common with LAMR1, Gal-3 binds the meningococcal secretin PilQ, in addition to the major pilin PilE. This study adds significant new mechanistic insights into the bacterial–host cell interaction by clarifying the nature, role and bacterial ligands of LAMR1 and Gal-3 isotypes during colonization. |
| Databáze: | OpenAIRE |
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