. Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) by ectodomain shedding and γ-secretase dependent intramembranous cleavage. J Biol Chem. 2013 Nov 15;288(46):33027-36. PubMed.


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  1. As far as it goes, this paper is quite provocative. The main limitations are that the experiments were done in artificial cell lines and used transfected molecular components. It should be possible, based on these findings, to demonstrate abnormalities of signaling in myeloid cells from individuals (or mice) harboring presenilin 1 mutations. Gamma secretase inhibition should also impair DAP12 signaling in primary myeloid cells. In summary, this study represents an excellent "discovery" exercise that generates important testable hypotheses.

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