Crosstalk between membrane trafficking and cell adhesion:The role of the SNARE protein TI-VAMP in neuronal morphogenesis

The membrane trafficking pathway mediated by the SNARE protein Tetanus neurotoxin-Insensitive Vesicle Associated Membrane Protein (TI-VAMP) in neurons is still unknown. In this work, I show that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells in culture. TI-VAMP interacts with plasma membrane and endosomal target SNAREs suggesting that TI-VAMP mediates a recycling pathway. This view is supported by the direct demonstration that TI-VAMP recycles from and to the plasma membrane. L1, a cell-cell adhesion molecule involved in axonal outgrowth, colocalizes with TI-VAMP in the developing brain, neurons in culture, and PC12 cells. Plasma membrane L1 is internalized into the TI-VAMP-containing compartment. Silencing of TI-VAMP results in reduced expression of L1 at the plasma membrane and impaired L1- but not N-Cadherin-mediated adhesion. Futhermore, the TI-VAMP-compartment is specifically recruited to L1 bead-cell junctions in an actin-dependent manner suggesting that axon guidance cues like L1-ligation act by controlling cytoskeletal and membrane dynamics in a coordinated manner. In conclusion, TI-VAMP mediates the intracellular transport of L1 and L1-mediated adhesion controls this membrane trafficking, thereby suggesting that cross-talk between membrane trafficking and cell-cell adhesion plays a central role in coordinating axonal outgrowth and pathfinding