Unconventional SNARE In The ER 1 (USE1)

D12 is a SNARE protein that binds to syntaxin-18, Sec22b, alpha-SNAP, and VAMP7, thus showing that D12 interacts with SNARES involved in the early and the post-Golgi secretory apparatus and with endosome-lysosome transport. Immunofluorescence and siRNA assays showed that neither overexpression nor knockdown of D12 affected ER, Golgi, or ER-Golgi intermediate compartment structures, suggesting that D12 does not regulate membrane trafficking in the early secretory pathway. However, D12 knockdown did induce apoptosis, as measured by condensed nuclear chromatin, caspase-3 activation, and BAX conformational change. In addition, D12 downregulation caused rapid appearance of lipofuscin granules, suggesting impaired degradation of mitochondria by lysosomal degradative enzymes.