The TREM-receptor family interactome in the human brain

Proteomics of human AD and non-AD brain lysates identified novel interactors for TREML1 and TREML2, including APOA1/APOA4 and heparan sulfate–modified proteins.

• Why it matters: While TREM2 ligands and binding partners are linked to Alzheimer disease, the ligand binding partners of other TREM family members remain poorly defined.
• What they did: The study profiled the interactome of ligand binding domains for TREM1, TREM2, TREML1, TREML2, and TREML4 using human AD and non-AD brain lysate proteomics, plus in vitro heparin pulldowns.
• The result: TREML1 interacted with complement components and apolipoproteins APOA1 and APOA4, while TREML2 bound heparan sulfate modified proteins; TREML2–heparan sulfate binding was unaffected by the AD-linked S144G mutation.