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Molecular and Cellular Biology, August 2007, p. 5699-5710, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.00383-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

Departments of Molecular Biology and Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, California 92037,¹ Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 ul. Miklukho-Maklaya, 117997 Moscow, Russia,² Institute for Biological Sciences, National Research Council, Ottawa, Ontario K1A OR6, Canada,³ Division of Cell Biology and Immunology, The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom⁴

Received 2 March 2007/ Returned for modification 15 April 2007/ Accepted 1 June 2007

Sialic acid-binding immunoglobulin-like lectins (siglecs) are predominately expressed on immune cells. They are best known as regulators of cell signaling mediated by cytoplasmic tyrosine motifs and are increasingly recognized as receptors for pathogens that bear sialic acid-containing glycans. Most siglec proteins undergo endocytosis, an activity tied to their roles in cell signaling and innate immunity. Here, we investigate the endocytic pathways of two siglec proteins, CD22 (Siglec-2), a regulator of B-cell signaling, and mouse eosinophil Siglec-F, a member of the rapidly evolving CD33-related siglec subfamily that are expressed on cells of the innate immune system. CD22 exhibits hallmarks of clathrin-mediated endocytosis and traffics to recycling compartments, consistent with previous reports demonstrating its localization to clathrin domains. Like CD22, Siglec-F mediates endocytosis of anti-Siglec-F and sialoside ligands, a function requiring intact tyrosine-based motifs. In contrast, however, we find that Siglec-F endocytosis is clathrin and dynamin independent, requires ADP ribosylation factor 6, and traffics to lysosomes. The results suggest that these two siglec proteins have evolved distinct endocytic mechanisms consistent with roles in cell signaling and innate immunity.

Published ahead of print on 11 June 2007.

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