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Deciphering the complex three-way interaction between the non-integrin laminin receptor, galectin-3 and Neisseria meningitidis

Alqahtani, Fulwah Yahya Saleh; Mahdavi, Jafar; Wheldon, Lee M.; Vassey, Matthew; Pirinccioglu, Necmettin; Royer, Pierre-Joseph; Qarani, Suzan M.; Morroll, Shaun; Stoof, Jeroen; Holliday, Nicholas D.; Teo, Siew Y.; Oldfield, Neil J.; Wooldridge, Karl G.; Ala'Aldeen, Dlawer A.A.

Authors

Fulwah Yahya Saleh Alqahtani

Jafar Mahdavi

Lee M. Wheldon

Necmettin Pirinccioglu

Pierre-Joseph Royer

Suzan M. Qarani

Shaun Morroll

Jeroen Stoof

Nicholas D. Holliday

Siew Y. Teo

Neil J. Oldfield

Karl G. Wooldridge

Dlawer A.A. Ala'Aldeen



Abstract

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 (C173) of Gal-3 or lysine (K166) 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.

Journal Article Type Article
Publication Date Oct 1, 2014
Journal Open Biology
Electronic ISSN 2046-2441
Publisher Royal Society, The
Peer Reviewed Peer Reviewed
Volume 4
Issue 10
Article Number 140053
APA6 Citation Alqahtani, F. Y. S., Mahdavi, J., Wheldon, L. M., Vassey, M., Pirinccioglu, N., Royer, P., …Ala'Aldeen, D. A. (2014). Deciphering the complex three-way interaction between the non-integrin laminin receptor, galectin-3 and Neisseria meningitidis. Open Biology, 4(10), https://doi.org/10.1098/rsob.140053
DOI https://doi.org/10.1098/rsob.140053
Keywords LAMR1, RPSA, galectin-3, 37LRP, 67LR, Neisseria meningitidis
Publisher URL http://rsob.royalsocietypublishing.org/content/4/10/140053
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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