Abstract
Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons.
Highlights
Neurons are specialized for directional transfer of information, and require unique sets of membrane proteins in axonal and dendritic regions
To determine whether plasma membrane SNAREs could contribute to the polarized trafficking of membrane proteins in neurons, we investigated the distribution pattern of the plasma membrane syntaxins 3 and 4 in mature hippocampal neurons by examining the distribution of myc-tagged Stx3 and Stx4 and green fluorescent protein (GFP) using transient adenovirus-mediated expression (Fig 1A)
By investigating the targeting of axonal and dendritic proteins in hippocampal neurons, our studies indicate that Stx3, a plasma membrane t-SNARE, participates in the targeted delivery of axonal cargos
Summary
Neurons are specialized for directional transfer of information, and require unique sets of membrane proteins in axonal and dendritic regions. Establishment and maintenance of neuronal polarity depends on precise targeting of proteins to functional sites in specialized neuronal subdomains [1,2,3,4]. How neurons achieve a polarized distribution of membrane proteins remains an intriguing and challenging question. Several mechanisms have been proposed to act at successive stages along the secretory and endocytic pathway to ensure the fidelity of polarized trafficking [1,2,3,4,5,6]. PLOS ONE | DOI:10.1371/journal.pone.0163671 September 23, 2016
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