AUTHOR=Karyu Hitomi , Niki Takahiro , Sorimachi Yuriko , Hata Shoji , Shimabukuro-Demoto Shiho , Hirabayashi Tetsuya , Mukai Kojiro , Kasahara Kohji , Takubo Keiyo , Goda Nobuhito , Honke Koichi , Taguchi Tomohiko , Sorimachi Hiroyuki , Toyama-Sorimachi Noriko 

TITLE=Collaboration between a cis-interacting natural killer cell receptor and membrane sphingolipid is critical for the phagocyte function

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1401294

DOI=10.3389/fimmu.2024.1401294

ISSN=1664-3224

ABSTRACT=<p>Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in <italic>trans</italic> on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in <italic>cis</italic>, but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in <italic>cis</italic> and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells. We identified a lipid-binding motif in the juxtamembrane region of Ly49Q and found that Ly49Q organized functional membrane domains comprising sphingolipids via sulfatide binding. Ly49Q recruited actin-remodeling molecules to an immunoreceptor tyrosine-based inhibitory motif, which enabled the sphingolipid-enriched membrane domain to mediate complicated actin remodeling at the lamellipodia and phagosome membranes during phagocytosis. Thus, Ly49Q facilitates integrative regulation of proteins and lipid species to construct a cell type-specific membrane platform. Other Ly49 members possess lipid binding motifs; therefore, membrane platform organization may be a primary role of some NK cell receptors.</p>