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A pH ‐ and ionic strength‐dependent conformational change in the neck region regulates DNGR ‐1 function in dendritic cells
Author(s) -
Hanč Pavel,
Schulz Oliver,
Fischbach Hanna,
Martin Stephen R,
Kjær Svend,
Reis e Sousa Caetano
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694695
Subject(s) - library science , computer science
DNGR ‐1 is receptor expressed by certain dendritic cell ( DC ) subsets and by DC precursors in mouse. It possesses a C‐type lectin‐like domain ( CTLD ) followed by a poorly characterized neck region coupled to a transmembrane region and short intracellular tail. The CTLD of DNGR ‐1 binds F‐actin exposed by dead cell corpses and causes the receptor to signal and potentiate cross‐presentation of dead cell‐associated antigens by DC s. Here, we describe a conformational change that occurs in the neck region of DNGR ‐1 in a pH ‐ and ionic strength‐dependent manner and that controls cross‐presentation of dead cell‐associated antigens. We identify residues in the neck region that, when mutated, lock DNGR ‐1 in one of the two conformational states to potentiate cross‐presentation. In contrast, we show that chimeric proteins in which the neck region of DNGR ‐1 is replaced by that of unrelated C‐type lectin receptors fail to promote cross‐presentation. Our results suggest that the neck region of DNGR ‐1 is an integral receptor component that senses receptor progression through the endocytic pathway and has evolved to maximize extraction of antigens from cell corpses, coupling DNGR ‐1 function to its cellular localization.