Siglec-15

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Siglec-15 serves as a paradigm for several siglecs, including Siglec-14[1], Siglec-16[2] and Siglec-H[3][4], that contain a basic amino acid within the transmembrane domain[5]. This leads to association of these siglecs with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM). Siglec-15 is unusual compared to other siglecs that share this paradigm in two respects. Firstly it can associate with two ITAM containing adaptors, DAP12 and DAP10, whereas Siglec-14, Siglec-16, and Siglec-H show a restricted association with DAP12. Siglec-15 is also unusual in having four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs. These potentially ‘activating’ siglecs are expressed on myeloid cells and dendritic cells and may be involved in innate responses to pathogen challenge.

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

As yet, no CFG Participating Investigators (PIs) have contributed to Siglec-15, but contributors to the related Siglec-H include Marco Colonna and Paul Crocker.

Progress toward understanding this GBP paradigm

Carbohydrate ligands


Cellular expression


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for Siglec-15.

Glycan profiling


Glycogene microarray


Knockout mouse lines

The CFG has generated Siglec-15-deficient ES cells that will permit generation of a Siglec-15-deficient mouse in the future. Two Siglec-H-deficient mouse lines (Siglec-H-conditional knockout and Siglec-H-total knockout) were also generated and are currently under investigation.

Glycan array

Related GBPs

Siglec-14, Siglec-16, Siglec-H

References

  1. Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. Faseb J 20, 1964-1973 (2006).
  2. Cao, H. et al. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur J Immunol 38, 2303-2315 (2008).
  3. Zhang, J. et al. Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107, 3600-3608 (2006).
  4. Blasius, A. L., Cella, M., Maldonado, J., Takai, T. & Colonna, M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).
  5. Delputte, P. L. et al. Porcine arterivirus attachment to the macrophage-specific receptor sialoadhesin is dependent on the sialic81, 9546-9550 (2007).

Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Takashi Angata, Paul Crocker, James Paulson

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