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Neuron. 2018 May 16;98(4):767-782.e8. doi: 10.1016/j.neuron.2018.04.011. Epub 2018 May 3.

Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase.

Author information

1
Department of Neuroscience and Jefferson Synaptic Biology Center, The Vickie and Jack Farber Institute, Jefferson Hospital for Neuroscience, Thomas Jefferson University, Suite 461, 900 Walnut Street, Philadelphia, PA 19107, USA.
2
Department of Neuroscience and Jefferson Synaptic Biology Center, The Vickie and Jack Farber Institute, Jefferson Hospital for Neuroscience, Thomas Jefferson University, Suite 461, 900 Walnut Street, Philadelphia, PA 19107, USA; Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi City, Gunma 371-8511, Japan.
3
Department of Neurobiology, Harvard Medical School, Room 336 Warren Alpert Building, 220 Longwood Avenue, Boston, MA 02115, USA.
4
Department of Neuroscience and Jefferson Synaptic Biology Center, The Vickie and Jack Farber Institute, Jefferson Hospital for Neuroscience, Thomas Jefferson University, Suite 461, 900 Walnut Street, Philadelphia, PA 19107, USA. Electronic address: matthew.dalva@jefferson.edu.

Abstract

Dendritic filopodia select synaptic partner axons by interviewing the cell surface of potential targets, but how filopodia decipher the complex pattern of adhesive and repulsive molecular cues to find appropriate contacts is unknown. Here, we demonstrate in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. Super-resolution and live-cell imaging reveals that EphB2 is located in the tips of filopodia and at nascent synaptic sites. Surprisingly, a genetically encoded indicator of EphB kinase activity, unbiased classification, and a photoactivatable EphB2 reveal that simple differences in the kinetics of EphB kinase signaling at the tips of filopodia mediate the choice between retraction and synaptogenesis. This may enable individual filopodia to choose targets based on differences in the activation rate of a single tyrosine kinase, greatly simplifying the process of partner selection and suggesting a general principle.

KEYWORDS:

cell signaling; kinase reporter; modeling; neuronal development; optogenetics; photoactivation; synaptogenesis; technology development; transfectable indicator

PMID:
29731254
PMCID:
PMC5987257
[Available on 2019-05-16]
DOI:
10.1016/j.neuron.2018.04.011

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