Skip to main content

Flotillin-2 (FLOT2)

  • Reference work entry
  • First Online:
Encyclopedia of Signaling Molecules
  • 188 Accesses

Synonyms

Epidermal surface antigen (ESA); ESA1; Membrane component, Chromosome 17, Surface marker 1 (M17S1); Reggie-1 (Reg-1)

Historical Background

Flotillin-2 was originally cloned in 1994 by Schroeder et al. by immunoscreening of a human keratinocyte cDNA library using the monoclonal antibody ECS-1 against cultured keratinocytes. ECS-1 stained human epidermis and caused keratinocyte detachment in vitro, leading to the hypothesis that ECS-1 antigen may play a role in epidermal cell adhesion. Therefore, the immunoisolated cDNA and deduced protein was termed “epidermal surface antigen” (ESA), reviewed in Langhorst et al. (2005) and Morrow and Parton (2005). Western blot analysis identified a 35 kDa protein. In 1997, Bickel et al. analyzed caveolin-rich membrane fractions from mouse lung and isolated a 45 kDa protein. Microsequencing yielded novel and ESA-specific peptide sequences. Degenerate primers were used for PCR of mouse lung cDNA, and the PCR product was then used as a probe for...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Babuke T, Ruonala M, Meister M, Amaddii M, Genzler C, Esposito A, Tikkanen R. Hetero-oligomerization of reggie- 1/flotillin-2 and reggie-2/flotillin-1 is required for their endocytosis. Cell Signal. 2009;21:1287–97.

    Article  PubMed  CAS  Google Scholar 

  • Banning A, Kurrle N, Meister M, Tikkanen R. Flotillins in receptor tyrosine kinase signaling and cancer. Cells. 2014;3:129–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bodin S, Planchon D, Rios Morris E, Comunale F, Gauthier-Rouvière C. Flotillins in intercellular adhesion - from cellular physiology to human diseases. J Cell Sci. 2014;127:5139–47.

    Article  PubMed  CAS  Google Scholar 

  • Frick M, Bright NA, Riento K, Bray A, Merrified C, Nichols BJ. Coassembly of flotillins induces formation of membrane microdomains, membrane curvature, and vesicle budding. Curr Biol. 2007;17:1151–6.

    Article  PubMed  CAS  Google Scholar 

  • Ge L, Qi W, Wang LJ, Miao HH, Qu YX, Li BL, Song BL. Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake. Proc Natl Acad Sci U S A. 2011;108:551–6.

    Article  PubMed  Google Scholar 

  • Guillaume E, Comunale F, Do Khoa N, Planchon D, Bodin S, Gauthier-Rouvière C. Flotillin microdomains stabilize cadherins at cell-cell junctions. J Cell Sci. 2013;126:5293–304.

    Article  PubMed  CAS  Google Scholar 

  • Juarez MT, Patterson RA, Sandoval-Guillen E, McGinnis W. Duox, Flotillin-2, and Src42A are required to activate or delimit the spread of the transcriptional response to epidermal wounds in Drosophila. PLoS Genet. 2011;7:e1002424.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Katanaev VL, Solis GP, Hausmann G, Buestorf S, Katanayeva N, Schrock Y, Stuermer CA, Basler K. Reggie-1/flotillin-2 promotes secretion of the long-range signalling forms of wingless and Hedgehog in Drosophila. EMBO J. 2008;27:509–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kurrle N, Völlner F, Eming R, Hertl M, Banning A, Tikkanen R. Flotillins directly interact with gamma-catenin and regulate epithelial cell-cell adhesion. PLoS One. 2013;8:e84393.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Langhorst MF, Reuter A, Stuermer CA. Scaffolding microdomains and beyond: the function of reggie/flotillin proteins. Cell Mol Life Sci. 2005;62:2228–40.

    Article  PubMed  CAS  Google Scholar 

  • Langhorst MF, Reuter A, Jaeger FA, Wippich FM, Luxenhofer G, Plattner H, Stuermer CA. Trafficking of the microdomain scaffolding protein reggie-1/flotillin-2. Eur J Cell Biol. 2008;87:211–26.

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Martin BR, Cravatt BF, Hofmann SL. DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells. J Biol Chem. 2012;287:523–530.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu J, Huang W, Ren C, Wen Q, Liu W, Yang X, Wang L, Zhu B, Zeng L, Feng X, Zhang C, Chen H, Jia W, Zhang L, Xia X, Chen Y. Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-kappa B and PI3K/Akt3 signaling pathways. Sci Rep. 2015;5:11614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ludwig A, Otto GP, Riento K, Hams E, Fallon PG, Nichols BJ. Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment. J Cell Biol. 2010;191:771–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meister M, Tikkanen R. Endocytic trafficking of membrane-bound cargo: a flotillin point of view. Membranes. 2014;4:356–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meister M, Zuk A, Tikkanen R. Role of dynamin and clathrin in the cellular trafficking of flotillins. FEBS J. 2014;281:2956–76.

    Article  PubMed  CAS  Google Scholar 

  • Morrow IC, Parton RG. Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic. 2005;6:725–40.

    Article  PubMed  CAS  Google Scholar 

  • Neumann-Giesen C, Falkenbach B, Beicht P, Claasen S, Lüers G, Stuermer CA, Herzog V, Tikkanen R. Membrane and raft association of reggie-1/flotillin-2: role of myristoylation, palmitoylation and oligomerization and induction of filopodia by overexpression. Biochem J. 2004;378:509–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Neumann-Giesen C, Fernow I, Amaddii M, Tikkanen R. Role of EGF-induced tyrosine phosphorylation of reggie-1/flotillin-2 in cell spreading and signaling to the actin cytoskeleton. J Cell Sci. 2007;120:395–406.

    Article  PubMed  CAS  Google Scholar 

  • Otto GP, Nichols BJ. The roles of flotillin microdomains - endocytosis and beyond. J Cell Sci. 2011;124:3933–40.

    Article  PubMed  CAS  Google Scholar 

  • Rajendran L, Masilamani M, Solomon S, Tikkanen R, Stuermer CA, Plattner H, Illges H. Asymmetric localization of flotillins/reggies in preassembled platforms confers inherent polarity to hematopoietic cells. Proc Natl Acad Sci U S A. 2003;100:8241–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rajendran L, Beckmann J, Magenau A, Boneberg EM, Gaus K, Viola A, Giebel B, Illges H. Flotillins are involved in the polarization of primitive and mature hematopoietic cells. PLoS One. 2009;4:e8290.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Riento K, Frick M, Schafer I, Nichols BJ. Endocytosis of flotillin-1 and flotillin-2 is regulated by Fyn kinase. J Cell Sci. 2009;122:912–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rivera-Milla E, Stuermer CA, Málaga-Trillo E. Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain. Cell Mol Life Sci. 2006;63:343–57.

    Article  PubMed  CAS  Google Scholar 

  • Rossy J, Schlicht D, Engelhardt B, Niggli V. Flotillins interact with PSGL-1 in neutrophils and, upon stimulation, rapidly organize into membrane domains subsequently accumulating in the uropod. PLoS One. 2009;4:e5403.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Salzer U, Prohaska R. Flotillin 2. UCSD nature molecule pages. 2011. doi:10.1038/mp.a002226.01

    Google Scholar 

  • Sasaki Y, Oshima Y, Koyama R, Maruyama R, Akashi H, Mita H, Toyota M, Shinomura Y, Imai K, Tokino T. Identification of flotillin-2, a major protein on lipid rafts, as a novel target of p53 family members. Mol Cancer Res. 2008;6:395–406.

    Article  PubMed  CAS  Google Scholar 

  • Schneider J, Mielich-Suss B, Bohme R, Lopez D. In vivo characterization of the scaffold activity of flotillin on the membrane kinase KinC of Bacillus subtilis. Microbiology. 2015;161:1871–87.

    Article  PubMed  CAS  Google Scholar 

  • Solis GP, Hoegg M, Munderloh C, Schrock Y, Malaga-Trillo E, Rivera-Milla E, Stuermer CA. Reggie/flotillin proteins are organized into stable tetramers in membrane microdomains. Biochem J. 2007;403:313–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Solis GP, Hülsbusch N, Radon Y, Katanaev VL, Plattner H, Stuermer CA. Reggies/flotillins interact with Rab11a and SNX4 at the tubulovesicular recycling compartment and function in transferrin receptor and E-cadherin trafficking. Mol Biol Cell. 2013;24:2689–702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sugawara Y, Nishii H, Takahashi T, Yamauchi J, Mizuno N, Tago K, Itoh H. The lipid raft proteins flotillins/reggies interact with Galphaq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase. Cell Signal. 2007;19:1301–8.

    Article  PubMed  CAS  Google Scholar 

  • Swanwick CC, Shapiro ME, Yi Z, Chang K, Wenthold RJ. NMDA receptors interact with flotillin-1 and -2, lipid raft-associated proteins. FEBS Lett. 2009;583:1226–30.

    Article  PubMed  CAS  Google Scholar 

  • Völlner F, Ali J, Kurrle N, Exner Y, Eming R, Hertl M, Banning A, Tikkanen R. Loss of flotillin expression results in weakened desmosomal adhesion and Pemphigus vulgaris-like localisation of desmoglein-3 in human keratinocytes. Sci Rep. 2016;6:28820.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rainer Prohaska .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Prohaska, R., Salzer, U. (2018). Flotillin-2 (FLOT2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_646

Download citation

Publish with us

Policies and ethics