Deciphering a novel mechanism regulating galectin‐glycoprotein lattice assembly/disassembly during cell‐cell interactions
Authors: ELANTAK Latifa , Touarin Pauline , Bornet Olivier , Chen Qian , Scott Lincoln G. , Guerlesquin Francoise 
Published: June 2021

Multivalent protein‐carbohydrate interactions lead to the formation of lattices on cell surfaces which regulate essential cellular events, including cell adhesion, cell proliferation, modulation of cell signaling, cell death and pathogen recognition of host cells. Consequently, cells “fine‐tune” the regulation of these functions by modulating the assembly/disassembly of protein‐carbohydrate lattices. One family of multivalent lectins that can organize cell surface lattices is the galectins. Altering protein glycosylation or lectin expression are two well‐described ways for a cell to dynamically modulate the strength of the lectin‐glycoprotein lattice interactions. Here, we suggest a third new mechanism of modulation of such crucial interactions which we evidenced in the case of early B cell development. During B‐cell development, bone marrow stromal cells secreting galectin‐1 (Gal1) constitute a specific niche for pre‐BII cells. Besides binding glycans, Gal1 is also a pre‐B cell receptor (pre‐BCR) ligand which induces pre‐BCR clustering, the first checkpoint of B cell differentiation. The Gal1/pre‐BCR interaction is the first example of a Gal1/unglycosylated protein interaction in the extracellular compartment. We performed in‐depth NMR (nuclear magnetic resonance) structural characterization of this interaction (2) and showed that Gal1/pre‐BCR interaction modifies Gal1/glycan affinity towards specific glycan epitopes (1). NMR structural studies using 13C‐labeled glycan bound to Gal1 in the presence and in the absence of the pre‐BCR binding sequence revealed the structural basis of this new mechanism of regulation of Gal1 interactions. Moreover, our investigations led us to demonstrate that, while bound to stromal cell membranes, the carbohydrate binding site of Gal1 undergoes structural modifications in the presence of the pre‐BCR. These results provide evidence the Gal1/pre‐BCR interaction acts as a physiological regulator of the Gal1/glycoprotein lattice. Therefore, this fine tuning of GAL1/glycan interactions may be a strategic mechanism for allowing pre‐BCR activation and pre‐BII cells departure from their niche (1). But, beyond the pre‐BCR case, it was also tempting to wonder if Gal1 lattice modifications induced by binding to an unglycosylated protein sequence could be used in other Gal1 dependent processes in order to regulate specific cellular functions and responses. Therefore, we screened for other potential unglycosylated protein candidates for Gal1 binding and investigated there binding to Gal1 using NMR spectroscopy. The results obtained suggest that the protein interacting site on Gal1 serves as tuning platform of lattice assembly/disassembly for several signaling pathways and cellular processes.

Support or Funding Information

L. Elantak research is supported by the Agence Nationale de la Recherche (grant: ANR‐16‐CE11‐0005‐01)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.