Next Article in Journal
Nutrition and Cardiovascular Health
Next Article in Special Issue
The Implications for Cells of the Lipid Switches Driven by Protein–Membrane Interactions and the Development of Membrane Lipid Therapy
Previous Article in Journal
Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation
Previous Article in Special Issue
The Binding of Aβ42 Peptide Monomers to Sphingomyelin/Cholesterol/Ganglioside Bilayers Assayed by Density Gradient Ultracentrifugation
Open AccessReview

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

Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland
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;
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
Show Figures

Figure 1

MDPI and ACS Style

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop