Loss of Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein α (αSNAP) Induces Epithelial Cell Apoptosis via Down-regulation of Bcl-2 Expression and Disruption of the Golgi

Abstract

Background: Vesicle trafficking proteins play important roles in regulating cell survival. Results: Inhibition of a key membrane fusion protein, ␣SNAP, induced epithelial cell apoptosis, decreased Bcl-2 level, and impaired ER-Golgi communications. Conclusion: ␣SNAP promotes cell survival by controlling ER/Golgi-dependent expression of Bcl-2. Significance: Uncovering mechanisms that link vesicle trafficking and apoptosis is critical for understanding the regulation of cell fate.

Loss of a membrane trafficking protein αSNAP induces non-canonical autophagy in human epithelia

“…30,31 Since several recent studies suggested that the Golgi can supply membranes to the autophagic pathway, 12,14,37-39 we investigated if disintegration of this organelle can contribute to the increased autophagic flux in αSNAP-deficient cells. Using HeLa-GFP-LC3 cells, we observed that formation of autophagosomes after αSNAP knockdown occurred in parallel to fragmentation of both cys and trans-Golgi compartments as visualized by giantin and TGN46 labeling, respectively (Fig.…”

“…We have previously shown that knockdown of αSNAP has multiple effects on cultured epithelial cells, including induction of apoptosis. 31 Autophagy and apoptosis appeared to be orchestrated in SK-CO15 cells, as they occur simultaneously at 48 h of αSNAP knockdown (Fig. 1A).…”

“…Surprisingly, do not understand how loss of αSNAP results in the decreased expression of mTOR or 4E-BP1 as well as some other proteins (Bcl-2 and p120-catenin) described in our previous publications. 30,31 Future studies are required to address this important question.…”

“…They reinforce recently published data that other cellular functions of αSNAP, such as regulation of cell-cell adhesions and cell survival, do not depend on its interactions with NSF. 30,31 What is the biological significance of the enhanced autophagy in αSNAP-depleted cells? According to our results, it does not counteract the simultaneously induced apoptosis (Fig.…”

“…30,31 Although a key role of NSF in regulating yeast autophagy has been recently reported, 32 the involvement of αSNAP in autophagosomal biogenesis remains unexplored. The present study examines the role of αSNAP in regulating autophagy in model human epithelia.…”