The enigmatic nature of the triggering receptor expressed in myeloid cells -1 (TLT- 1)

Abstract

Receptors are important pharmacological targets on cells. The Triggering Receptor Expressed on Myeloid Cells (TREM) – Like Transcript – 1 is an abundant, yet little understood, platelet receptor. It is a single Ig domain containing receptor isolated in the α-granules of resting platelets and brought to the platelet surface upon activation. On platelets, the integrin αIIbβ3 is the major receptor having roughly 80,000 copies. αIIbβ3 is a heterodimeric multidomain structure that mediates platelet aggregation through its interaction with the plasma protein fibrinogen. Anti-platelet drugs have successfully targeted αIIbβ3 to control thrombosis. Like αIIbβ3, TLT-1 also binds fibrinogen, making its role in platelet function somewhat obscure. In this review, we highlight the known structural features of TLT-1 and present the challenges of understanding TLT-1 function. In our analysis of the dynamics of the platelet surface after activation we propose a model in which TLT-1 supports αIIbβ3 function as a mechanoreceptor that may direct platelets toward immune function.

Keywords:

• Blood platelets
• fibrinogen
• lungs
• neutrophils
• platelet receptors
• trem-Like transcript-1 (TLT-1)
• αIIbβ3

Acknowledgements

We would like to thank Dr Angela Gibson and Julia Warrick for their careful review and insightful comment during the preparation of this manuscript.

Sources of funding: NIH R01HL090933 and R21HL140268

Author Contribution

S. Branfield and A.V. Washington wrote the manuscript and revised each other’s contributions. Both authors have approved the final version.

Disclosure

A.V. Washington has been granted a patent on TLT-1 antibodies and therapeutic uses thereof.