Microtubule Motors Power Plasma Membrane Tubulation in Clathrin-Independent Endocytosis

Charles A. Day, Nicholas W. Baetz, Courtney A. Copeland, Lewis J. Kraft, Bing Han, Ajit Tiwari, Kimberly R. Drake, Heidi De Luca, Daniel J.F. Chinnapen, Michael W. Davidson, Randall K. Holmes, Michael G. Jobling, Trina A. Schroer, Wayne I. Lencer, Anne K. Kenworthy

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

How the plasma membrane is bent to accommodate clathrin-independent endocytosis remains uncertain. Recent studies suggest Shiga and cholera toxin induce membrane curvature required for their uptake into clathrin-independent carriers by binding and cross-linking multiple copies of their glycosphingolipid receptors on the plasma membrane. But it remains unclear if toxin-induced sphingolipid crosslinking provides sufficient mechanical force for deforming the plasma membrane, or if host cell factors also contribute to this process. To test this, we imaged the uptake of cholera toxin B-subunit into surface-derived tubular invaginations. We found that cholera toxin mutants that bind to only one glycosphingolipid receptor accumulated in tubules, and that toxin binding was entirely dispensable for membrane tubulations to form. Unexpectedly, the driving force for tubule extension was supplied by the combination of microtubules, dynein and dynactin, thus defining a novel mechanism for generating membrane curvature during clathrin-independent endocytosis.

Original languageEnglish (US)
Pages (from-to)572-590
Number of pages19
JournalTraffic
Volume16
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Cholera toxin
  • Clathrin-independent endocytosis
  • Dynactin
  • Dynein
  • Membrane curvature
  • Microtubules

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    Day, C. A., Baetz, N. W., Copeland, C. A., Kraft, L. J., Han, B., Tiwari, A., Drake, K. R., De Luca, H., Chinnapen, D. J. F., Davidson, M. W., Holmes, R. K., Jobling, M. G., Schroer, T. A., Lencer, W. I., & Kenworthy, A. K. (2015). Microtubule Motors Power Plasma Membrane Tubulation in Clathrin-Independent Endocytosis. Traffic, 16(6), 572-590. https://doi.org/10.1111/tra.12269