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Sterol Flow between the Plasma Membrane and the Endosome is Regulated by the LAM Family Protein Ltc1

49 Pages Posted: 23 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Magdalena Marek

Magdalena Marek

University of Lausanne - Department of Fundamental Microbiology

Vincent Vincenzetti

University of Lausanne - Department of Fundamental Microbiology

Sophie G. Martin

University of Lausanne - Department of Fundamental Microbiology

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Abstract

Sterols are crucial components of biological membranes that help maintain membrane integrity and regulate various processes such as endocytosis, protein oligomerization and signaling. Although synthetized in the ER, sterols are at highest concentrations at the plasma membrane (PM) in all eukaryotic organisms. Here, by applying a genetically encoded sterol biosensor (D4H), we visualize a sterol flow between PM and endosomes in the fission yeast Schizosaccharomyces pombe. While D4H is detected at the PM during steady-state growth, inhibition of Arp2/3-dependent F-actin assembly unexpectedly promotes the reversible re-localization of the probe to internal sterol rich compartments (STRIC), as shown by correlative light-electron microscopy. Time-lapse imaging identifies STRIC as a late secretory, endosomal compartment labelled by the synaptobrevin Syb1. Retrograde sterol internalization to STRIC is independent of endocytosis or an intact Golgi. Instead, it depends on Ltc1, a LAM/StARkin-family protein that localizes to ER-PM contact sites. In ltc1Δ, sterols over-accumulate at the PM, which forms extended ER-interacting invaginations, indicating that sterol transfer by Ltc1 contributes to PM size homeostasis. Anterograde sterol movement from STRIC is independent of canonical vesicular trafficking components but requires Arp2/3 activity, suggesting a novel physiological role for this complex. Thus, transfer routes orthogonal to vesicular trafficking govern the retrograde and anterograde flow of sterols in the cell.

Keywords: sterol trafficking, lipid transfer protein, ER-PM contact sites, fission yeast Schizosaccharomyces pombe, ergosterol, actin, Arp2/3

Suggested Citation

Marek, Magdalena and Vincenzetti, Vincent and Martin, Sophie G., Sterol Flow between the Plasma Membrane and the Endosome is Regulated by the LAM Family Protein Ltc1 (August 23, 2019). DEVELOPMENTAL-CELL-D-19-00701. Available at SSRN: https://ssrn.com/abstract=3441419 or http://dx.doi.org/10.2139/ssrn.3441419
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Magdalena Marek

University of Lausanne - Department of Fundamental Microbiology

Lausanne
Switzerland

Vincent Vincenzetti

University of Lausanne - Department of Fundamental Microbiology

Lausanne
Switzerland

Sophie G. Martin (Contact Author)

University of Lausanne - Department of Fundamental Microbiology ( email )

Lausanne
Switzerland

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