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J. Cell Biol.,
Volume 140, Number 1, January 12, 1998 223-232
The formation of a growth cone at the tip of
a transected axon is a crucial step in the subsequent regeneration of the amputated axon. During this process,
the transected axon is transformed from a static segment into a motile growth cone. Despite the importance of this process for regeneration of the severed
axon, little is known about the mechanisms underlying
this transformation.
Recent studies have suggested that Ca2+-activated
proteinases underlay the morphological remodeling of
neurons after injury. However, this hypothesis was
never tested directly. Here we tested the ability of transient and localized increases in intracellular proteolytic
activity to induce growth cone formation and neuritogenesis. Minute amounts of the proteinase trypsin were
microinjected into intact axonal segments or somata of
cultured Aplysia neurons, transiently elevating the intracellular protease concentration to 13-130 nM in the
vicinity of the injection site. Such microinjections were
followed by the formation of ectopic growth cones and
irreversible neuritogenesis. Growth cones were not
formed after external application of trypsin, microinjection of the carrier solution, or inactivated trypsin.
Growth cone formation was not preceded by increases
in free intracellular Ca2+ or changes in passive membrane properties, and was blocked by inhibitors of actin
and tubulin polymerization. Trypsin-induced neuritogenesis was associated with ultrastructural alterations similar to those observed by us after axotomy.
We conclude that local and transient elevations of cytoplasmic proteolytic activity can induce growth cone
formation and neuritogenesis, and suggest that localized proteolytic activity plays a role in growth cone formation after axotomy.
Department of Neurobiology, Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem 91904, Israel;
and * the Interuniversity Institute for Marine Science, Eilat, Israel
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