Cross Talk between Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein-mediated Transport and L1-mediated Adhesion

• DOI: 10.1091/mbc.e03-03-0147
• Publication Date: 2003-07-01T00:25:02Z
• Authors: Philipp Alberts; Rachel Rudge; Ina Hinners; Aude Muzerelle; Sonia Martinez-Arca; Theano Irinopoulou; Véronique Marthiens; Sharon Tooze; Fritz Rathjen; Patricia Gaspar; Thierry Galli
• Keywords: Neurons; 0303 health sciences; Microscopy, Video; Cell Membrane; Brain; Membrane Proteins; Biological Transport; Neural Cell Adhesion Molecule L1; Cadherins; Cytoplasmic Granules; Embryo, Mammalian; PC12 Cells; Cell Compartmentation; Protein Structure, Tertiary; R-SNARE Proteins; Mice; 03 medical and health sciences; Neurites; Animals; RNA, Small Interfering; Function and Dysfunction of the Nervous System; Cells, Cultured; Protein Binding

The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells and hippocampal neurons in culture. TI-VAMP interacts with plasma membrane and endosomal target soluble N-ethylmaleimide-sensitive factor attachment protein receptors, suggesting that TI-VAMP mediates a recycling pathway. L1, a cell-cell adhesion molecule involved in axonal outgrowth, colocalized with TI-VAMP in the developing brain, neurons in culture, and PC12 cells. Plasma membrane L1 was internalized into the TI-VAMP–containing compartment. Silencing of TI-VAMP resulted in reduced expression of L1 at the plasma membrane. Finally, using the extracellular domain of L1 and N-cadherin immobilized on beads, we found that the silencing of TI-VAMP led to impaired L1- but not N-cadherin–mediated adhesion. Furthermore, TI-VAMP- but not synaptobrevin 2-containing vesicles accumulated at the site of the L1 bead-cell junction. We conclude that TI-VAMP mediates the intracellular transport of L1 and that L1-mediated adhesion controls this membrane trafficking, thereby suggesting an important cross talk between membrane trafficking and cell-cell adhesion.