In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-12-22)
Abstract:
Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.31101.001
DOI:
10.7554/eLife.31101.002
DOI:
10.7554/eLife.31101.003
DOI:
10.7554/eLife.31101.004
DOI:
10.7554/eLife.31101.005
DOI:
10.7554/eLife.31101.006
DOI:
10.7554/eLife.31101.007
DOI:
10.7554/eLife.31101.008
DOI:
10.7554/eLife.31101.009
DOI:
10.7554/eLife.31101.010
DOI:
10.7554/eLife.31101.011
DOI:
10.7554/eLife.31101.012
DOI:
10.7554/eLife.31101.013
DOI:
10.7554/eLife.31101.014
DOI:
10.7554/eLife.31101.015
DOI:
10.7554/eLife.31101.016
DOI:
10.7554/eLife.31101.017
DOI:
10.7554/eLife.31101.018
DOI:
10.7554/eLife.31101.019
DOI:
10.7554/eLife.31101.020
DOI:
10.7554/eLife.31101.021
DOI:
10.7554/eLife.31101.022
DOI:
10.7554/eLife.31101.023
DOI:
10.7554/eLife.31101.024
DOI:
10.7554/eLife.31101.025
DOI:
10.7554/eLife.31101.026
DOI:
10.7554/eLife.31101.027
DOI:
10.7554/eLife.31101.028
DOI:
10.7554/eLife.31101.029
DOI:
10.7554/eLife.31101.033
DOI:
10.7554/eLife.31101.034
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3