Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery

Ting Ya Chang, Chen Chen, Min Lee, Ya Chu Chang, Chi Huan Lu, Shao Tzu Lu, De Yao Wang, Aijun Wang, Chin Lin Guo, Pei Lin Cheng

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article numbere31101
JournaleLife
Volume6
DOIs
StatePublished - Dec 22 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Chang, T. Y., Chen, C., Lee, M., Chang, Y. C., Lu, C. H., Lu, S. T., Wang, D. Y., Wang, A., Guo, C. L., & Cheng, P. L. (2017). 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