UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic
components from dendrites
Vivian Y. Poon1, Matthew P. Klassen1 & Kang Shen1,2
1. Neuroscience Program, Stanford University School of Medicine,
300 Pasteur Drive, California 94305, USA
2. Department of Biology, Howard Hughes Medical Institute, Stanford
University, 385 Serra Mall, California 94305, USA
Correspondence to: Kang Shen1,2 Correspondence and requests for
materials should be addressed to K.S. (Email:
kang...@stanford.edu).
Polarity is an essential feature of many cell types, including neurons
that receive information from local inputs within their dendrites and
propagate nerve impulses to distant targets through a single axon. It
is generally believed that intrinsic structural differences between
axons and dendrites dictate the polarized localization of axonal and
dendritic proteins1. However, whether extracellular cues also instruct
this process in vivo has not been explored. Here we show that the axon
guidance cue UNC-6/netrin and its receptor UNC-5 act throughout
development to exclude synaptic vesicle and active zone proteins from
the dendrite of the Caenorhabditis elegans motor neuron DA9, which is
proximal to a source of UNC-6/netrin. In unc-6/netrin and unc-5 loss-
of-function mutants, presynaptic components mislocalize to the DA9
dendrite. In addition, ectopically expressed UNC-6/netrin, acting
through UNC-5, is sufficient to exclude endogenous synapses from
adjacent subcellular domains within the DA9 axon. Furthermore, this
anti-synaptogenic activity is interchangeable with that of LIN-44/Wnt
despite being transduced through different receptors, suggesting that
extracellular cues such as netrin and Wnts not only guide axon
navigation but also regulate the polarized accumulation of presynaptic
components through local exclusion.
http://www.nature.com/nature/journal/v455/n7213/abs/nature07291.html