NGF-activated protein tyrosine phosphatase 1B mediates the phosphorylation and degradation of I-κ-Bα coupled to NF-κ-B activation, thereby controlling dendrite morphology

Chacon Fernandez, Pedro, Arévalo, María Ángeles and Tébar, Alfredo Rodríguez 2010. NGF-activated protein tyrosine phosphatase 1B mediates the phosphorylation and degradation of I-κ-Bα coupled to NF-κ-B activation, thereby controlling dendrite morphology. Molecular and Cellular Neuroscience 43 (4) , pp. 384-393. 10.1016/j.mcn.2010.01.005

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Abstract

NGF diminishes dendrite complexity in cultured hippocampal neurons by decreasing the number of primary and secondary dendrites, while increasing the length of those that remain. The transduction pathway used by NGF to provoke dendrite elongation involves the activation of NF-κ-B and the expression of the homologues of Enhancer-of-split 1gene. Here, we define important steps that link NGF with NF-κ-B activation, through the activity of protein tyrosine phosphatase 1B (PTP1B). Binding of NGF to p75NTR stimulates PTP1B activity, which can be blocked by either pharmacological inhibition of the phosphatase or by transfecting neurons with a dnPTP1B isoform, whereby NGF is no longer able to stimulate dendrite growth. Indeed, overexpressing PTP1B alone provoked dendrite growth and further studies revealed a role for the src kinase downstream of PTP1B. Again, loss of src activity largely cancelled out the capacity of NGF to promote dendrite growth, whereas overexpression of v-src in neurons was sufficient to promote dendrite growth. Finally, the NGF/p75NTR/PTP1B/src kinase pathway led to the tyrosine phosphorylation of I-κ-Bα prior to its degradation, an event that is necessary for NF-κ-B activation. Indeed, the dendrite growth response to NGF was lost when neurons were transfected with a mutant form of I-κ-Bα that lacks tyr42. Thus, our data suggest that PTP1B fulfils a central role in the NGF signalling that controls dendrite patterning in hippocampal neurons.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	1044-7431
Last Modified:	28 Jun 2019 02:01
URI:	https://orca.cardiff.ac.uk/id/eprint/65865

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