UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Control of Axonal Growth and Regeneration of Sensory Neurons by the p110 delta PI 3-Kinase

Eickholt, BJ; Ahmed, AI; Davies, M; Papakonstanti, EA; Pearce, W; Starkey, ML; Bilando, A; ... Vanhaesebroeck, B; + view all (2007) Control of Axonal Growth and Regeneration of Sensory Neurons by the p110 delta PI 3-Kinase. PLOS ONE , 2 (9) , Article e869. 10.1371/journal.pone.0000869. Green open access

[thumbnail of journal.pone.0000869.pdf]
Preview
PDF
journal.pone.0000869.pdf

Download (479kB)

Abstract

The expression and function of the 8 distinct catalytic isoforms of PI 3-kinase (P13K) in the nervous system are unknown. Whereas most P13Ks have a broad tissue distribution, the tyrosine kinase-linked p110 delta isoform has previously been shown to be enriched in leukocytes. Here we report that p110 delta is also highly expressed in the nervous system. Inactivation of p110 delta in mice did not affect gross neuronal development but led to an increased vulnerability of dorsal root ganglia neurons to exhibit growth cone collapse and decreases in axonal extension. Loss of p110 delta activity also dampened axonal regeneration following peripheral nerve injury in adult mice and impaired functional recovery of locomotion. p110 delta inactivation resulted in reduced neuronal signaling through the Akt protein kinase, and increased activity of the small GTPase RhoA. Pharmacological inhibition of ROCK, a downstream effector of RhoA, restored axonal extension defects in neurons with inactive p110 delta, suggesting a key role of RhoA in p110 delta signaling in neurons. Our data identify p110 delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system.

Type: Article
Title: Control of Axonal Growth and Regeneration of Sensory Neurons by the p110 delta PI 3-Kinase
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0000869
Publisher version: http://dx.doi.org/10.1371/journal.pone.0000869
Language: English
Additional information: © 2007 Eickholt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/1419435
Downloads since deposit
56Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item