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Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

1
Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland
2
Institute of Biochemistry, Faculty of Biology, University of Warsaw, 2 Miecznikowa St., 02-096 Warsaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(7), 2283; https://doi.org/10.3390/ijms21072283
Received: 28 February 2020 / Revised: 19 March 2020 / Accepted: 20 March 2020 / Published: 26 March 2020
(This article belongs to the Special Issue Lipid-Protein and Protein-Protein Interactions in Membranes)
Flotillin-1 and flotillin-2 are ubiquitously expressed, membrane-associated proteins involved in multifarious cellular events from cell signaling, endocytosis, and protein trafficking to gene expression. They also contribute to oncogenic signaling. Flotillins bind the cytosolic leaflet of the plasma membrane and endomembranes and, upon hetero-oligomerization, serve as scaffolds facilitating the assembly of multiprotein complexes at the membrane–cytosol interface. Additional functions unique to flotillin-1 have been discovered recently. The membrane-binding of flotillins is regulated by S-palmitoylation and N-myristoylation, hydrophobic interactions involving specific regions of the polypeptide chain and, to some extent, also by their oligomerization. All these factors endow flotillins with an ability to associate with the sphingolipid/cholesterol-rich plasma membrane domains called rafts. In this review, we focus on the critical input of lipids to the regulation of the flotillin association with rafts and thereby to their functioning. In particular, we discuss how the recent developments in the field of protein S-palmitoylation have contributed to the understanding of flotillin1/2-mediated processes, including endocytosis, and of those dependent exclusively on flotillin-1. We also emphasize that flotillins affect directly or indirectly the cellular levels of lipids involved in diverse signaling cascades, including sphingosine-1-phosphate and PI(4,5)P2. The mutual relations between flotillins and distinct lipids are key to the regulation of their involvement in numerous cellular processes. View Full-Text
Keywords: flotillin; phosphatidylinositol; rafts; S-palmitoylation; sphingosine flotillin; phosphatidylinositol; rafts; S-palmitoylation; sphingosine
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Kwiatkowska, K.; Matveichuk, O.V.; Fronk, J.; Ciesielska, A. Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling. Int. J. Mol. Sci. 2020, 21, 2283.

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