Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery
- Academia Sinica, Taiwan, Republic of China
- University of California, Davis, United States
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.
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Funding
Ministry of Science and Technology, Taiwan (Research Grant)
- Pei-Lin Cheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kang Shen, Stanford University, United States
Version history
- Received: August 9, 2017
- Accepted: December 20, 2017
- Accepted Manuscript published: December 22, 2017 (version 1)
- Accepted Manuscript updated: December 23, 2017 (version 2)
- Version of Record published: January 15, 2018 (version 3)
Copyright
© 2017, Chang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery
eLife 6:e31101.
https://doi.org/10.7554/eLife.31101
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