Building and shaping tiny tubes: repurposing a cell-cell fusogen for membrane trafficking

Cell-cell fusogens of the Fusexin structural family mediate membrane merging during viral infection, fertilization, and formation of syncytial tissues. These types of membrane merging events initiate on the exoplasmic (non-cytosolic) side of a cell’s plasma membrane, and fuse two separate cells into one. Within an individual cell, some membrane trafficking events, including endocytic scission, also involve membrane merging that initiates on the exoplasmic side of the membrane, but how such fusion and fission occurs is not well understood. We discovered that the C. elegans Fusexin protein AFF-1 is required for endocytic scission and apically-directed trafficking during morphogenesis of a very narrow unicellular tube. This work expands the potential roles of cell-cell fusogens to intracellular membrane trafficking and suggests a new way to think about the basic process of endocytic scission: that in addition to relying on proteins that assemble on the cytosolic side and constrict and pinch the membrane, scission may utilize mechanisms similar to those involved in cell and vesicle fusion, where interactions between transmembrane fusogens help pull membranes into very close proximity for merging.