Transforming Growth Factor beta 1 Alters Synapsin Distribution and Modulates Synaptic Depression in Aplysia

Transforming growth factor beta 1 (TGF- beta 1) induces long-term synaptic facilitation and long-term increases in excitability in Aplysia. Here we report that this growth factor has acute effects as well. Treatment of pleural-pedal ganglia with TGF- beta 1 for 5 min activated mitogen-activated protein kinase (MAPK) and stimulated the phosphorylation of synapsin in a MAPK-dependent manner. This phosphorylation appeared to modulate synapsin distribution in cultured sensory neurons. Control neurons exhibited a punctate distribution of synapsin along neurites, which appeared to represent high concentration aggregates of synapsin. TGF- beta 1-treated sensory neurons showed a significant reduction in the number of these puncta, an effect that was blocked by the MAP/ERK kinase inhibitor U0126. The functional consequence of TGF- beta 1 was tested by examining its effects on synaptic transmission at the sensorimotor synapse. Application of TGF- beta 1 reduced the magnitude of synaptic depression. This effect was dependent on MAPK, consistent with the hypothesis that TGF- beta 1 mobilizes synaptic vesicles through the phosphorylation of synapsin.