Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• DNAX-activating protein of 12kDa (DAP12) is a type I transmembrane adapter protein.
• DAP12 contains immunoreceptor tyrosine-based activation motifs (ITAMs) and is encoded on human chromosome 19q13.1.
• DAP12 forms a complex with the triggering receptor expressed on myeloid cells two (TREM-2).

Purpose of the Study:

• To review the structure, biological functions, and signaling pathways of DAP12.
• To discuss the role of the DAP12/TREM-2 complex in cellular processes.
• To highlight the challenges in understanding TREM-2 ligand interactions.

Main Methods:

• Literature review of existing research on DAP12 and TREM-2.
• Analysis of signaling pathways initiated by TREM-2 ligation.
• Examination of the cellular functions regulated by the DAP12/TREM-2 complex.

Main Results:

• TREM-2 ligation activates Src family kinases, leading to DAP12 ITAM phosphorylation.
• This recruits Syk and ZAP70 tyrosine kinases, initiating intracellular signaling.
• The DAP12/TREM-2 complex is involved in osteoclast differentiation, phagocytosis, homeostasis, and TLR signaling inhibition.

Conclusions:

• The DAP12/TREM-2 complex plays diverse roles in myeloid cell function and tissue homeostasis.
• Understanding the signaling cascade is vital for comprehending immune responses.
• Further research into TREM-2 ligands is needed to fully elucidate complex functions.