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Sci Adv. 2015 Sep 11;1(8):e1500301. doi: 10.1126/sciadv.1500301.

Dynamic spectrin/ankyrin-G microdomains promote lateral membrane assembly by opposing endocytosis.

Author information

1
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
3
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA ; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA ; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA ; Howard Hughes Medical Institute, Durham, NC 27710, USA.

Abstract

Current physical models for plasma membranes emphasize dynamic 10- to 300-nm compartments at thermodynamic equilibrium but subject to thermal fluctuations. However, epithelial lateral membranes contain micrometer-sized domains defined by an underlying membrane skeleton composed of spectrin and its partner ankyrin-G. We demonstrate that these spectrin/ankyrin-G domains exhibit local microtubule-dependent movement on a time scale of minutes and encounter most of the lateral membranes within an hour. Spectrin/ankyrin-G domains exclude clathrin and clathrin-dependent cargo, and inhibit both receptor-mediated and bulk endocytosis. Moreover, inhibition of endocytosis fully restores lateral membrane height in spectrin- or ankyrin-G-depleted cells. These findings support a non-equilibrium cellular-scale model for epithelial lateral membranes, where spectrin/ankyrin-G domains actively patrol the plasma membrane, analogous to "window washers," and promote columnar morphology by blocking membrane uptake.

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