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Neuronal growth cone retraction relies on proneurotrophin receptor signaling through rac

Neuronal growth cone retraction relies on proneurotrophin receptor signaling through rac
Neuronal growth cone retraction relies on proneurotrophin receptor signaling through rac
Growth of axons and dendrites is a dynamic process that involves guidance molecules, adhesion
proteins, and neurotrophic factors. Although neurite extension during development has been
extensively studied, the intracellular mechanisms that mediate neurite retraction are poorly
understood. Here, we show that the proneurotrophin, proNGF, induces acute collapse of growth
cones of cultured hippocampal neurons. This retraction is initiated by an interaction between
p75NTR and the sortilin family member, SorCS2 (sortilin-related VPS10 domain containing
receptor 2). Binding of proNGF to the p75NTR-SorCS2 complex induced growth cone retraction
by initiating the dissociation of the guanine-nucleotide exchange factor Trio from the p75NTRSorCS2
complex, resulting in decreased Rac activity, and consequently, growth cone collapse.
The actin-bundling protein fascin also became inactivated, contributing to the destabilization and
collapse of actin filaments. These results identify a bifunctional signaling mechanism by which
proNGF regulates actin dynamics to modulate neuronal morphology acutely.
p.ra82
Deinhardt, K.
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Kim, T.
8d6a5974-2a5b-434e-8ddf-488ff188ddc2
Spellman, D.S.
82409252-a5eb-466e-93ff-0bd0ac2afe58
Mains, R.E.
74a2fe97-eb4f-44e2-9e68-521034194831
Eipper, B.A.
1a92f2a8-b984-4f61-81a8-65c82f7bb833
Neubert, T.A.
edeb695e-0ace-423e-867b-465513d4fbb3
Chao, M.V.
eae54f43-a2d5-4c0e-a16d-2f78a3d0369c
Hempstead, B.L.
870332bb-3d5b-4577-818c-c972722673b9
Deinhardt, K.
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Kim, T.
8d6a5974-2a5b-434e-8ddf-488ff188ddc2
Spellman, D.S.
82409252-a5eb-466e-93ff-0bd0ac2afe58
Mains, R.E.
74a2fe97-eb4f-44e2-9e68-521034194831
Eipper, B.A.
1a92f2a8-b984-4f61-81a8-65c82f7bb833
Neubert, T.A.
edeb695e-0ace-423e-867b-465513d4fbb3
Chao, M.V.
eae54f43-a2d5-4c0e-a16d-2f78a3d0369c
Hempstead, B.L.
870332bb-3d5b-4577-818c-c972722673b9

Deinhardt, K., Kim, T., Spellman, D.S., Mains, R.E., Eipper, B.A., Neubert, T.A., Chao, M.V. and Hempstead, B.L. (2011) Neuronal growth cone retraction relies on proneurotrophin receptor signaling through rac. Science Signaling, 4 (202), p.ra82. (doi:10.1126/scisignal.2002060).

Record type: Article

Abstract

Growth of axons and dendrites is a dynamic process that involves guidance molecules, adhesion
proteins, and neurotrophic factors. Although neurite extension during development has been
extensively studied, the intracellular mechanisms that mediate neurite retraction are poorly
understood. Here, we show that the proneurotrophin, proNGF, induces acute collapse of growth
cones of cultured hippocampal neurons. This retraction is initiated by an interaction between
p75NTR and the sortilin family member, SorCS2 (sortilin-related VPS10 domain containing
receptor 2). Binding of proNGF to the p75NTR-SorCS2 complex induced growth cone retraction
by initiating the dissociation of the guanine-nucleotide exchange factor Trio from the p75NTRSorCS2
complex, resulting in decreased Rac activity, and consequently, growth cone collapse.
The actin-bundling protein fascin also became inactivated, contributing to the destabilization and
collapse of actin filaments. These results identify a bifunctional signaling mechanism by which
proNGF regulates actin dynamics to modulate neuronal morphology acutely.

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Published date: December 2011
Organisations: Faculty of Natural and Environmental Sciences, Centre for Biological Sciences

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Local EPrints ID: 345195
URI: http://eprints.soton.ac.uk/id/eprint/345195
PURE UUID: a5560842-d061-4b40-93d9-747451c99495
ORCID for K. Deinhardt: ORCID iD orcid.org/0000-0002-6473-5298

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Date deposited: 13 Nov 2012 10:25
Last modified: 03 Dec 2019 01:37

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