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Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient
Published on: September 3, 2014
UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites
Vivian Y Poon1, Matthew P Klassen, Kang Shen
1Neuroscience Program, Stanford University School of Medicine, 300 Pasteur Drive, California 94305, USA.
Nature
|September 9, 2008
Summary
Extracellular cues like netrin and Wnt guide neuron polarity. These signals prevent presynaptic components from accumulating in dendrites, ensuring proper neuron function.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Neuronal polarity, essential for function, is thought to be determined by intrinsic structural differences between axons and dendrites.
- The role of extracellular cues in establishing and maintaining neuronal polarity in vivo remains largely unexplored.
Purpose of the Study:
- To investigate the in vivo role of extracellular cues in instructing the polarized localization of presynaptic components in neurons.
- To determine if axon guidance cues influence the exclusion of synaptic proteins from dendrites.
Main Methods:
- Utilized the Caenorhabditis elegans motor neuron DA9 as a model system.
- Investigated the function of the axon guidance cue UNC-6/netrin and its receptor UNC-5.
- Analyzed loss-of-function mutants for unc-6/netrin and unc-5.
- Examined the effects of ectopic UNC-6/netrin expression.
Main Results:
- UNC-6/netrin and UNC-5 actively exclude synaptic vesicle and active zone proteins from the DA9 dendrite.
- Loss of UNC-6/netrin or UNC-5 leads to mislocalization of presynaptic components into the DA9 dendrite.
- Ectopic UNC-6/netrin expression excludes synapses from specific subcellular domains within the axon.
- The anti-synaptogenic activity of netrin is interchangeable with LIN-44/Wnt, despite different receptors.
Conclusions:
- Extracellular cues, including netrin and Wnt, play a crucial role in regulating the polarized distribution of presynaptic components.
- These cues establish neuronal polarity not only by guiding axon navigation but also by mediating local exclusion of synaptic material.
- Neuronal polarity is established through a combination of intrinsic factors and external signaling pathways.
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