title: A TREM family member, TLT-1, is found exclusively in the alpha-granules of megakaryocytes and platelets.
abstract: The triggering receptors expressed on myeloid cells (TREMs) have drawn considerable attention due to their ability to activate multiple cell types within the innate immune system, including neutrophils, monocyte/macrophages, and dendritic cells, via their association with DAP12. TLT-1 (TREM-like transcript-1) lies within the TREM gene cluster and contains the characteristic single V-set immunoglobulin (Ig) domain of the family, but its longer cytoplasmic tail is composed of both a proline-rich region and an immune receptor tyrosine-based inhibitory motif, the latter known to be used for interactions with protein tyrosine phosphatases. Here we report that TLT-1 is expressed exclusively in platelets and megakaryocytes (MKs) and that TLT-1 expression is up-regulated dramatically upon platelet activation. Consistent with this observation, confocal microscopy demonstrates that TLT-1 is prepackaged, along with CD62P, into both MK and platelet alpha-granules. Differences in thrombin-induced redistribution of CD62P and TLT-1 indicate that TLT-1 is not simply cargo of alpha-granules but may instead regulate granule construction or dispersal. Together these data show that that TLT-1 does not function to inhibit members of the TREM family but instead may play a role in maintaining vascular hemostasis and regulating coagulation and inflammation at sites of injury.
authors.affiliation: NCI-Frederick, 560/Rm 31-46, Frederick, MD 21702, USA.
authors.forename: A Valance
authors.initials: AV
authors.lastname: Washington
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Schubert
authors.forename: Laura
authors.initials: L
authors.lastname: Quigley
authors.forename: Theresa
authors.initials: T
authors.lastname: Disipio
authors.forename: Robert
authors.initials: R
authors.lastname: Feltz
authors.forename: Edward H
authors.initials: EH
authors.lastname: Cho
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000737:chemistry* / Q000648:ultrastructure; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000737:chemistry*; D006801:Humans; D008533:Megakaryocytes / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D018613:Microscopy, Confocal; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D019007:P-Selectin; D011971:Receptors, Immunologic; C471763:Treml1 protein, mouse; D013917:Thrombin