Cross-talk between membrane fusion, cell cycle, and apoptosis

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The NSF-α-SNAP-SNAREs complex is a large protein complex implicated in membrane fusion between transport vesicles and their target membranes. We have recently discovered an endoplasmic reticulum (ER) SNARE, syntaxin 18, and demonstrated that this protein forms a complex with ZW10 (a kinetochore protein involved in spindle checkpoint), RINT-1 (G2/M checkpoint protein), and BNIP1 (a member of the pro-apoptotic BH3-only family). The purpose of this research is to elucidate the mechanisms underlying cross-talk between membrane fusion, cell-cycle, and apoptosis via the syntaxin 18 complex. The following results have been obtained.1)Interactions between components of the syntaxin 18 complexTwo-hybrid analysis revealed the interactions between syntaxin 18 and p31, RINT-1 and ZW10, and RINT-1 and BNIP1. RINT-1, ZW10 and p31 form a sub-complex.2)Involvement of ZW10 in membrane traffic between the ER and GolgiOverexpression, knockdown, and microinjection studies revealed that ZW10 in the interphase plays a role in membrane trafficking between the ER and Golgi.3)Implication of BNIP1 in ER-ER membrane fusionBNIP1 was found to participate in ER-ER membrane fusion, rather than membrane transport between the ER and Golgi. Binding studies revealed that Leu-114, a highly conserved residue in the pro-apoptotic BH3 domain of BNIP1, is essential for the interaction with α-SNAP but not with RINT-1. Overexpression of α-SNAP markedly delayed staurosporine-induced apoptosis. These results raise the possibility that BNIP1 functions in cross-talk between membrane fusion and apoptosis.