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PTEN couples Sema3A signalling to growth cone collapse

PTEN couples Sema3A signalling to growth cone collapse
PTEN couples Sema3A signalling to growth cone collapse
Distinct changes in glycogen synthase kinase-3 (GSK-3) signalling can regulate neuronal morphogenesis including the determination and maintenance of axonal identity, and are required for neurotrophin-mediated axon elongation. In addition, we have previously shown a dependency on GSK-3 activation in the semaphorin 3A (Sema3A)-mediated growth-cone-collapse response of sensory neurons. Regulation of GSK-3 activity involves the intermediate signalling lipid phosphatidylinositol 3,4,5-trisphosphate, which can be modulated by phosphatidylinositol 3-kinase (PI3K) and the tumour suppressor PTEN. We report here the involvement of PTEN in the Sema3A-mediated growth cone collapse. Sema3A suppresses PI3K signalling concomitant with the activation of GSK-3, which depends on the phosphatase activity of PTEN. PTEN is highly enriched in the axonal compartment and the central domain of sensory growth cones during axonal extension, where it colocalises with microtubules. Following exposure to Sema3A, PTEN accumulates rapidly at the growth cone membrane suggesting a mechanism by which PTEN couples Sema3A signalling to growth cone collapse. These findings demonstrate a dependency on PTEN to regulate GSK-3 signalling in response to Sema3A and highlight the importance of subcellular distributions of PTEN to control growth cone behaviour.
0021-9533
951-957
Chadborn, Neil H
3c3f0e0f-2d6c-4c71-bdfa-d7ab59f34f25
Ahmed, Aminul I.
175a1358-5255-4f20-8cf9-96fac237bc9f
Holt, Mark R
644f060e-11ce-429b-a927-bede1c117e10
Prinjha, Rabinder
236b0ae9-ce6b-45b9-9a09-1bd61be0b2be
Dunn, Graham A
cce77e93-4258-433a-816c-732f4a296c46
Jones, Gareth E
7cdbb05d-9dea-4507-9df8-308cb8271b1e
Eickholt, Britta J
01480969-5e50-48b1-9942-584bfef49e90
Chadborn, Neil H
3c3f0e0f-2d6c-4c71-bdfa-d7ab59f34f25
Ahmed, Aminul I.
175a1358-5255-4f20-8cf9-96fac237bc9f
Holt, Mark R
644f060e-11ce-429b-a927-bede1c117e10
Prinjha, Rabinder
236b0ae9-ce6b-45b9-9a09-1bd61be0b2be
Dunn, Graham A
cce77e93-4258-433a-816c-732f4a296c46
Jones, Gareth E
7cdbb05d-9dea-4507-9df8-308cb8271b1e
Eickholt, Britta J
01480969-5e50-48b1-9942-584bfef49e90

Chadborn, Neil H, Ahmed, Aminul I., Holt, Mark R, Prinjha, Rabinder, Dunn, Graham A, Jones, Gareth E and Eickholt, Britta J (2006) PTEN couples Sema3A signalling to growth cone collapse. Journal of Cell Science, 119 (5), 951-957. (doi:10.1242/jcs.02801). (PMID:16495486)

Record type: Article

Abstract

Distinct changes in glycogen synthase kinase-3 (GSK-3) signalling can regulate neuronal morphogenesis including the determination and maintenance of axonal identity, and are required for neurotrophin-mediated axon elongation. In addition, we have previously shown a dependency on GSK-3 activation in the semaphorin 3A (Sema3A)-mediated growth-cone-collapse response of sensory neurons. Regulation of GSK-3 activity involves the intermediate signalling lipid phosphatidylinositol 3,4,5-trisphosphate, which can be modulated by phosphatidylinositol 3-kinase (PI3K) and the tumour suppressor PTEN. We report here the involvement of PTEN in the Sema3A-mediated growth cone collapse. Sema3A suppresses PI3K signalling concomitant with the activation of GSK-3, which depends on the phosphatase activity of PTEN. PTEN is highly enriched in the axonal compartment and the central domain of sensory growth cones during axonal extension, where it colocalises with microtubules. Following exposure to Sema3A, PTEN accumulates rapidly at the growth cone membrane suggesting a mechanism by which PTEN couples Sema3A signalling to growth cone collapse. These findings demonstrate a dependency on PTEN to regulate GSK-3 signalling in response to Sema3A and highlight the importance of subcellular distributions of PTEN to control growth cone behaviour.

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Published date: 1 March 2006

Identifiers

Local EPrints ID: 183439
URI: https://eprints.soton.ac.uk/id/eprint/183439
ISSN: 0021-9533
PURE UUID: ad3df867-fa75-4ea9-9a6d-8b721b2d2e4b

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Date deposited: 11 May 2011 09:17
Last modified: 18 Jul 2017 11:55

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Contributors

Author: Neil H Chadborn
Author: Aminul I. Ahmed
Author: Mark R Holt
Author: Rabinder Prinjha
Author: Graham A Dunn
Author: Gareth E Jones
Author: Britta J Eickholt

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