Essential role of the Ly49A stalk region for immunological synapse formation and signaling
NK cells use surface NK receptors to discriminate self from non-self. The NK receptor ligand-binding domain (NKD) has been considered the sole regulator of ligand binding. Using a prototypic murine NK receptor, Ly49A, we show that the membrane proximal nonligand binding ecto-domain (the stalk region...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 27; pp. 11264 - 11269 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
07.07.2009
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | NK cells use surface NK receptors to discriminate self from non-self. The NK receptor ligand-binding domain (NKD) has been considered the sole regulator of ligand binding. Using a prototypic murine NK receptor, Ly49A, we show that the membrane proximal nonligand binding ecto-domain (the stalk region) is critical to ligand binding and signaling. The stalk region is required for receptor binding to ligand on target cells (trans interaction), but is dispensable for receptor binding to ligand on the same cell (cis interaction). Also, signaling in a trans manner depends on the stalk region mediating the formation of the immunological synapse. Thus, our data modeling receptor function at the cellular level reveal an essential role for the stalk region as a specific mediator of receptor signal integration, by which NKD-ligand interactions at the interface initiate and deliver information to the spatially separated cytoplasmic domain. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Wayne M. Yokoyama, Washington University School of Medicine, St. Louis, MO, and approved March 10, 2009 Author contributions: D.I. and K.I. designed research; D.I., Y.-M.I., and M.P.K. performed research; Y.-M.I. and K.I. contributed new reagents/analytic tools; D.I. and K.I. analyzed data; and D.I. and K.I. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0900664106 |