Mutations in Synaptojanin Disrupt Synaptic Vesicle Recycling

doi:10.1083/jcb.150.3.589

Published online 7 August 2000. doi:10.1083/jcb.150.3.589

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© The Rockefeller University Press, 0021-9525/2000//589 $5.00
The Journal of Cell Biology, Volume 150, Number 3, , 2000 589-600

Original Article

Mutations in Synaptojanin Disrupt Synaptic Vesicle Recycling

Todd W. Harris^a, Erika Hartwieg^b, H. Robert Horvitz^b, and Erik M. Jorgensen^a

^a Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840
^b Department of Biology, Massachussetts Institute of Technology, Cambridge, Massachusetts 02139
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112-0840.801 581-4668801 585-3517

jorgensen{at}biology.utah.edu

Synaptojanin is a polyphosphoinositide phosphatase that is foundat synapses and binds to proteins implicated in endocytosis.For these reasons, it has been proposed that synaptojanin isinvolved in the recycling of synaptic vesicles. Here, we demonstratethat the unc-26 gene encodes the Caenorhabditis elegans orthologof synaptojanin. unc-26 mutants exhibit defects in vesicle traffickingin several tissues, but most defects are found at synaptic termini.Specifically, we observed defects in the budding of synapticvesicles from the plasma membrane, in the uncoating of vesiclesafter fission, in the recovery of vesicles from endosomes, andin the tethering of vesicles to the cytoskeleton. Thus, theseresults confirm studies of the mouse synaptojanin 1 mutants,which exhibit defects in the uncoating of synaptic vesicles(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 synaptojanin facilitates multiplesteps of synaptic vesicle recycling.

Key Words: Caenorhabditis elegans • synaptic transmission • endocytosis • unc-26 • polyphosphoinositide phosphatase

Abbreviations used in this paper: Ce-synaptojanin, Caenorhabditiselegans synaptojanin; EST, expressed sequence tag; GABA, ${gamma}$ -aminobutyricacid; GFP, green fluorescent protein; ORF, open reading frame;PI, phosphoinositide.

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