Mutations in synaptojanin disrupt synaptic vesicle recycling

Synaptojanin is a polyphosphoinositide phosphatase that is found at synapse s and binds to proteins implicated in endocytosis. For these reasons, it ha s been proposed that synaptojanin is involved in the recycling of synaptic vesicles. Here, we demonstrate that the unc-26 gene encodes the Caenorhabdi tis elegans ortholog of synaptojanin. unc-26 mutants exhibit defects in ves icle trafficking in several tissues, but most defects are found at synaptic termini. Specifically, we observed defects in the budding of synaptic vesi cles from the plasma membrane, in the uncoating of vesicles after fission, in the recovery of vesicles from endosomes, and in the tethering of vesicle s to the cytoskele- ton. Thus, these results confirm studies of the mouse s ynaptojanin 1 mutants, which exhibit defects in the uncoating of synaptic v esicles (Cremona, O., G, Di Paolo, M.R, Wenk, A. Luthi, W.T. Kim, K. Takei, L. Daniell, Y. Nemoto, S,B, Shears, R.A. Flavell, D.A, McCormick, and P.De Camilli. 1999. Cell. 99:179-188), and further demonstrate that synaptojani n facilitates multiple steps of synaptic vesicle recycling.