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Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth

Bodmer, Daniel and Ascaño, Maria and Kuruvilla, Rejji. (2011) Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth. Neuron, Vol. 70, H. 6. pp. 1085-1099.

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Official URL: http://edoc.unibas.ch/dok/A6007009

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Abstract

Endocytic events are critical for neuronal survival in response to target-derived neurotrophic cues, but whether local axon growth is mediated by endocytosis-dependent signaling mechanisms remains unclear. Here, we report that Nerve Growth Factor (NGF) promotes endocytosis of its TrkA receptors and axon growth by calcineurin-mediated dephosphorylation of the endocytic GTPase dynamin1. Conditional deletion of calcineurin in sympathetic neurons disrupts NGF-dependent innervation of peripheral target tissues. Calcineurin signaling is required locally in sympathetic axons to support NGF-mediated growth in a manner independent of transcription. We show that calcineurin associates with dynamin1 via a PxIxIT interaction motif found only in specific dynamin1 splice variants. PxIxIT-containing dynamin1 isoforms colocalize with surface TrkA receptors, and their phosphoregulation is selectively required for NGF-dependent TrkA internalization and axon growth in sympathetic neurons. Thus, NGF-dependent phosphoregulation of dynamin1 is a critical event coordinating neurotrophin receptor endocytosis and axonal growth.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Inner Ear Research (Bodmer)
UniBasel Contributors:Bodmer, Daniel K
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0896-6273
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Sep 2013 07:59
Deposited On:13 Sep 2013 07:48

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