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Endocytosis-dependent desensitization and protein synthesis–dependent resensitization in retinal growth cone adaptation

Abstract

It has been proposed that growth cones navigating through gradients adapt to baseline concentrations of guidance cues. This adaptation process is poorly understood. Using the collapse assay, we show that adaptation in Xenopus laevis retinal growth cones to the guidance cues Sema3A or netrin-1 involves two processes: a fast, ligand-specific desensitization that occurs within 2 min of exposure and is dependent on endocytosis, and a slower, ligand-specific resensitization, which occurs within 5 min and is dependent upon protein synthesis. These two phases of adaptation allow retinal axons to adjust their range of sensitivity to specific guidance cues.

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Figure 1: Adaptation time course for retinal growth cones.
Figure 2: Adaptation adjusts sensitivity.
Figure 3: Resensitization is blocked by protein synthesis inhibitors.
Figure 4: Desensitization is blocked by endocytosis inhibitors.
Figure 5: Neuropilin-1 depletion and replacement in adaptation.
Figure 6: DCC depletion and replacement in adaptation.
Figure 7: Adaptation is ligand specific.

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Acknowledgements

We thank D. O'Connor, A. Dwivedy, D. Pask, S. Diamantakis, S. Shipway and E. Miranda for technical assistance, and K. Ohta and M. Tessier-Lavigne for the Sema3A and netrin-1 plasmids respectively. This work was supported by the Wellcome Trust and the Medical Research Council.

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Correspondence to William A Harris.

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Piper, M., Salih, S., Weinl, C. et al. Endocytosis-dependent desensitization and protein synthesis–dependent resensitization in retinal growth cone adaptation. Nat Neurosci 8, 179–186 (2005). https://doi.org/10.1038/nn1380

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