Drosophila Amphiphysin is a post-synaptic protein required for normal locomotion but not endocytosis.

Clathrin-mediated endocytosis is required to recycle synaptic vesicles for fast and efficient neurotransmission. Amphiphysins are thought to be multiprotein adaptors that may contribute to this process by bringing together many of the proteins required for endocytosis. Their in vivo function, however, has yet to be determined. Here, we show that the Drosophila genome encodes a single amphiphysin gene that is broadly expressed during development. We also show that, unlike its vertebrate counterparts, Drosophila Amphiphysin is enriched postsynaptically at the larval neuromuscular junction. To determine the role of Drosophila Amphiphysin, we also generated null mutants which are viable but give rise to larvae and adults with pronounced locomotory defects. Surprisingly, the locomotory defects cannot be accounted for by alterations in the morphology or physiology of the neuromuscular junction. Moreover, using stimulus protocols designed to test endocytosis under moderate and extreme vesicle cycling, we could not detect any defect in the neuromuscular junction of the amphiphysin mutant. Taken together, our findings suggest that Amphiphysin is not required for viability, nor is it absolutely required for clathrin-mediated endocytosis. However, Drosophila Amphiphysin function is required in both larvae and adults for normal locomotion.

Radiation-induced apoptosis in the adult central nervous system is p53-dependent.

Oligodendrocytes and subependymal cells in the adult CNS have been shown to undergo radiation-induced apoptosis. Here, we examined the role of p53 in radiation-induced apoptosis in the adult mouse CNS. In the spinal cord of p53+/+ mice, apoptotic glial cells were observed within 24 h after irradiation, and the apoptotic response peaked at 8 h. These apoptotic cells demonstrated the immunohistochemical phenotype of oligodendrocytes, and decreased oligodendrocyte density was observed at 24 h after 22 Gy. A similar time course of radiation-induced apoptosis was seen in subependymal cells in the adult mouse brain. Radiation-induced apoptosis was preceded by an increase in nuclear p53 expression in glial cells of the spinal cord and subependymal cells of the brain. There was no evidence of radiation-induced apoptosis in the spinal cord and subependymal region of p53-/- animals. We conclude that the p53 pathway may be a mechanism through which DNA damage induces apoptosis in the adult CNS.