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
Authors: Blasiak, Agata
Kilinc, Devrim
Lee, Gil U.
Permanent link: http://hdl.handle.net/10197/9605
Date: 5-Jan-2017
Online since: 2019-01-30T16:10:16Z
Abstract: 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.
Funding Details: European Commission - European Regional Development Fund
Science Foundation Ireland
Type of material: Journal Article
Publisher: Frontiers
Journal: Frontiers in Cellular Neuroscience
Volume: 10
Issue: 298
Copyright (published version): 2018 the Authors
Keywords: MicrofluidicsPath findingGuidance cuesCompartmentalizationCalcium signaling
DOI: 10.3389/fncel.2016.00298
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Chemistry Research Collection

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