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Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics

Netrin-1 modulates axonal growth direction and speed. Its best characterized receptor, Deleted in Colorectal Cancer (DCC), is localized to growth cones, but also observed in the cell bodies. We hypothesized that cell bodies sense Netrin-1 and contribute to axon growth rate modulation, mediated by th...

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Autores principales: Blasiak, Agata, Kilinc, Devrim, Lee, Gil U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214882/
https://www.ncbi.nlm.nih.gov/pubmed/28105005
http://dx.doi.org/10.3389/fncel.2016.00298
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author Blasiak, Agata
Kilinc, Devrim
Lee, Gil U.
author_facet Blasiak, Agata
Kilinc, Devrim
Lee, Gil U.
author_sort Blasiak, Agata
collection PubMed
description Netrin-1 modulates axonal growth direction and speed. Its best characterized receptor, Deleted in Colorectal Cancer (DCC), is localized to growth cones, but also observed in the cell bodies. We hypothesized that cell bodies sense Netrin-1 and contribute to axon growth rate modulation, mediated by the second messenger system. We cultured mouse cortical neurons in microfluidic devices to isolate distal axon and cell body microenvironments. Compared to isolated axonal treatment, global Netrin-1 treatment decreased the axon elongation rate and affected the dynamics of total and membranous DCC, calcium, and cyclic nucleotides. Signals induced by locally applied Netrin-1 propagated in both anterograde and retrograde directions, demonstrated by the long-range increase in DCC and by the increased frequency of calcium transients in cell bodies, evoked by axonal Netrin-1. Blocking the calcium efflux from endoplasmic reticulum suppressed the membranous DCC response. Our findings support the notion that neurons sense Netrin-1 along their entire lengths in making axonal growth decisions.
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spelling pubmed-52148822017-01-19 Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics Blasiak, Agata Kilinc, Devrim Lee, Gil U. Front Cell Neurosci Neuroscience Netrin-1 modulates axonal growth direction and speed. Its best characterized receptor, Deleted in Colorectal Cancer (DCC), is localized to growth cones, but also observed in the cell bodies. We hypothesized that cell bodies sense Netrin-1 and contribute to axon growth rate modulation, mediated by the second messenger system. We cultured mouse cortical neurons in microfluidic devices to isolate distal axon and cell body microenvironments. Compared to isolated axonal treatment, global Netrin-1 treatment decreased the axon elongation rate and affected the dynamics of total and membranous DCC, calcium, and cyclic nucleotides. Signals induced by locally applied Netrin-1 propagated in both anterograde and retrograde directions, demonstrated by the long-range increase in DCC and by the increased frequency of calcium transients in cell bodies, evoked by axonal Netrin-1. Blocking the calcium efflux from endoplasmic reticulum suppressed the membranous DCC response. Our findings support the notion that neurons sense Netrin-1 along their entire lengths in making axonal growth decisions. Frontiers Media S.A. 2017-01-05 /pmc/articles/PMC5214882/ /pubmed/28105005 http://dx.doi.org/10.3389/fncel.2016.00298 Text en Copyright © 2017 Blasiak, Kilinc and Lee. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Blasiak, Agata
Kilinc, Devrim
Lee, Gil U.
Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title_full Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title_fullStr Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title_full_unstemmed Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title_short Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
title_sort neuronal cell bodies remotely regulate axonal growth response to localized netrin-1 treatment via second messenger and dcc dynamics
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214882/
https://www.ncbi.nlm.nih.gov/pubmed/28105005
http://dx.doi.org/10.3389/fncel.2016.00298
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