Cross talk between tetanus neurotoxin-insensitive vesicle-associated membrane protein-mediated transport and L1-mediated adhesion.
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.
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000196:embryology / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism / Q000502:physiology; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000502:physiology; D004622:Embryo, Mammalian / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018715:Microscopy, Video; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism* / Q000502:physiology; D016501:Neurites / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D016716:PC12 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D050600:SNARE Proteins; D015398:Signal Transduction; D013347:Subcellular Fractions; D033921:Vesicular Transport Proteins
D015820:Cadherins; D008565:Membrane Proteins; D039842:Neural Cell Adhesion Molecule L1; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; D050600:SNARE Proteins; C496927:Sybl1 protein, mouse; C496926:Vamp7 protein, rat; D033921:Vesicular Transport Proteins