A common exocytotic mechanism mediates axonal and dendritic outgrowth

Outgrowth of the dendrites and the axon is the basis of the establishment o f the neuronal shape, and it requires addition of new membrane to both grow ing processes. It is not yet clear whether one or two exocytotic pathways a re responsible for the respective outgrowth of axons and dendrites. We have previously shown that tetanus neurotoxin-insensitive vesicle-associated me mbrane protein (TI-VAMP) defines a novel network of tubulovesicular structu res present both at the leading edge of elongating dendrites and axons of i mmature hippocampal neurons developing in primary culture and that TI-VAMP is an essential protein for neurite outgrowth in PC12 cells. Here we show t hat the expression of the N-terminal domain of TI-VAMP inhibits the outgrow th of both dendrites and axons in neurons in primary culture. This effect i s more prominent at the earliest stages of the development of neurons in vi tro. Expression of the N-terminal domain deleted form of TI-VAMP has the op posite effect. This constitutively active form of TI-VAMP localizes as the endogenous protein, particularly concentrating at the leading edge of growi ng axons. Our results suggest that a common exocytotic mechanism that relie s on TI-VAMP mediates both axonal and dendritic outgrowth in developing neu rons.