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Claudia A O Stuermer - One of the best experts on this subject based on the ideXlab platform.

  • reggie 1 Flotillin 2 regulates integrin trafficking and focal adhesion turnover via rab11a
    European Journal of Cell Biology, 2015
    Co-Authors: Nikola Hulsbusch, Gonzalo P Solis, Vladimir L Katanaev, Claudia A O Stuermer
    Abstract:

    Reggies/Flotillins are implicated in trafficking of membrane proteins to their target sites and in the regulation of the Rab11a-dependent targeted recycling of E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies in focal adhesion (FA) formation and α5- and β1-integrin recycling to FAs. Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased the number of FAs, impaired their distribution and modified FA turnover. This was coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects integrin trafficking emerged from the faster loss of internalized antibody-labeled β1-integrin in reggie-deficient cells. Moreover, live imaging using TIRF microscopy revealed vesicles containing reggie-1 and α5- or β1-integrin, trafficking close to the substrate-near membrane and making kiss-and-run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1 and FAK activation and coordinates the targeted recycling of α5- and β1-integrins to FAs to regulate FA formation and membrane dynamics.

  • upregulation of reggie 1 Flotillin 2 promotes axon regeneration in the rat optic nerve in vivo and neurite growth in vitro
    Neurobiology of Disease, 2013
    Co-Authors: Jan C Koch, Gonzalo P Solis, Vsevolod Bodrikov, Uwe Michel, Deana Haralampieva, Aleksandra Shypitsyna, Lars Tonges, Mathias Bahr, Paul Lingor, Claudia A O Stuermer
    Abstract:

    The ability of fish retinal ganglion cells (RGCs) to regenerate their axons was shown to require the re-expression and function of the two proteins reggie-1 and -2. RGCs in mammals fail to upregulate reggie expression and to regenerate axons after lesion suggesting the possibility that induced upregulation might promote regeneration. In the present study, RGCs in adult rats were induced to express reggie-1 by intravitreal injection of adeno-associated viral vectors (AAV2/1) expressing reggie-1 (AAV.R1-EGFP) 14d prior to optic nerve crush. Four weeks later, GAP-43-positive regenerating axons had crossed the lesion and grown into the nerve at significantly higher numbers and length (up to 5mm) than the control transduced with AAV.EGFP. Consistently, after transduction with AAV.R1-EGFP as opposed to AAV.EGFP, primary RGCs in vitro grew long axons on chondroitin sulfate proteoglycan (CSPG) and Nogo-A, both glial cell-derived inhibitors of neurite growth, suggesting that reggie-1 can provide neurons with the ability to override inhibitors of neurite growth. This reggie-1-mediated enhancement of growth was reproduced in mouse hippocampal and N2a neurons which generated axons 40-60% longer than their control counterparts. This correlates with the reggie-1-dependent activation of Src and PI3 kinase (PI3K), of the Rho family GTPase Rac1 and downstream effectors such as cofilin. This increased growth also depends on TC10, the GTPase involved in cargo delivery to the growth cone. Thus, the upregulation of reggie-1 in mammalian neurons provides nerve cells with neuron-intrinsic properties required for axon growth and successful regeneration in the adult mammalian CNS.

  • trafficking of the microdomain scaffolding protein reggie 1 Flotillin 2
    European Journal of Cell Biology, 2008
    Co-Authors: Matthias F Langhorst, Alexander Reuter, Georg Luxenhofer, Helmut Plattner, Friederike A Jaeger, Frank Wippich, Claudia A O Stuermer
    Abstract:

    The reggie/Flotillin proteins oligomerize and associate into clusters which form scaffolds for membrane microdomains. Besides their localization at the plasma membrane, the reggies/Flotillins reside at various intracellular compartments; however, the trafficking pathways used by reggie-1/Flotillin-2 remain unclear. Here, we show that trafficking of reggie-1/Flotillin-2 is BFA sensitive and that deletion mutants of reggie-1/Flotillin-2 accumulate in the Golgi complex in HeLa, Jurkat and PC12 cells, suggesting Golgi-dependent trafficking of reggie-1/Flotillin-2. Using total internal reflection fluorescence microscopy, we observed fast cycling of reggie-1/Flotillin-2-positive vesicles at the plasma membrane, which engaged in transient interactions with the plasma membrane only. Reggie-1/Flotillin-2 cycling was independent of clathrin, but was inhibited by cholesterol depletion and microtubule disruption. Cycling of reggie1/Flotillin-2 was negatively correlated with cell–cell contact formation but was stimulated by serum, epidermal growth factor and by cholesterol loading mediated by low density lipoproteins. However, reggie-1/Flotillin-2 was neither involved in endocytosis of the epidermal growth factor itself nor in endocytosis of GPI-GFPs or the GPI-anchored cellular prion protein (PrP c ). Reggie-2/Flotillin-1 and stomatin-1 also exhibited cycling at the plasma membrane similar to reggie-1/Flotillin-2, but these vesicles and microdomains only partially co-localized with reggie-2/Flotillin-1. Thus, regulated vesicular cycling might be a general feature of SPFH protein-dependent trafficking.

  • reggie 1 Flotillin 2 promotes secretion of the long range signalling forms of wingless and hedgehog in drosophila
    The EMBO Journal, 2008
    Co-Authors: Vladimir L Katanaev, Claudia A O Stuermer, Gonzalo P Solis, George Hausmann, Silke Buestorf, Natalya Katanayeva, Yvonne Schrock, Konrad Basler
    Abstract:

    The lipid-modified morphogens Wnt and Hedgehog diffuse poorly in isolation yet can spread over long distances in vivo, predicting existence of two distinct forms of these mophogens. The first is poorly mobile and activates short-range target genes. The second is specifically packed for efficient spreading to induce long-range targets. Subcellular mechanisms involved in the discriminative secretion of these two forms remain elusive. Wnt and Hedgehog can associate with membrane microdomains, but the function of this association was unknown. Here we show that a major protein component of membrane microdomains, reggie-1/Flotillin-2, plays important roles in secretion and spreading of Wnt and Hedgehog in Drosophila. Reggie-1 loss-of-function results in reduced spreading of the morphogens, while its overexpression stimulates secretion of Wnt and Hedgehog and expands their diffusion. The resulting changes in the morphogen gradients differently affect the short- and long-range targets. In its action reggie-1 appears specific for Wnt and Hedgehog. These data suggest that reggie-1 is an important component of the Wnt and Hedgehog secretion pathway dedicated to formation of the mobile pool of these morphogens.

  • linking membrane microdomains to the cytoskeleton regulation of the lateral mobility of reggie 1 Flotillin 2 by interaction with actin
    FEBS Letters, 2007
    Co-Authors: Matthias F Langhorst, Helmut Plattner, Gonzalo P Solis, Sylvia Hannbeck, Claudia A O Stuermer
    Abstract:

    The reggies/Flotillins are oligomeric scaffolding proteins for membrane microdomains. We show here that reggie-1/Flotillin-2 microdomains are organized along cortical F-actin in several cell types. Interaction with F-actin is mediated by the SPFH domain as shown by in vivo co-localization and in vitro binding experiments. Reggie-1/Flotillin-2 microdomains form independent of actin, but disruption or stabilization of the actin cytoskeleton modulate the lateral mobility of reggie-1/Flotillin-2 as shown by FRAP. Furthermore, reggie/Flotillin microdomains can efficiently be immobilized by actin polymerisation, while exchange of reggie-1/Flotillin-2 molecules between microdomains is enhanced by actin disruption as shown by tracking of individual microdomains using TIRF microscopy.

Ritva Tikkanen - One of the best experts on this subject based on the ideXlab platform.

  • Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase
    MDPI AG, 2018
    Co-Authors: Antje Banning, Melanie Meister, Nina Kurrle, Tanja Babuke, Mika O Ruonala, Ritva Tikkanen
    Abstract:

    Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and Flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for Flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that Flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by Flotillins. In the absence of Flotillins, especially Flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how Flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation

  • phosphatidylinositol 3 kinase dependent upregulation of the epidermal growth factor receptor upon Flotillin 1 depletion in breast cancer cells
    BMC Cancer, 2013
    Co-Authors: Nina Kurrle, Antje Banning, Melanie Meister, Wymke Ockenga, Frauke Vollner, Sina Kuhne, Bincy A John, Ritva Tikkanen
    Abstract:

    Background: Flotillin-1 and Flotillin-2 are two homologous and ubiquitously expressed proteins that are involved in signal transduction and membrane trafficking. Recent studies have reported that Flotillins promote breast cancer progression, thus making them interesting targets for breast cancer treatment. In the present study, we have investigated the underlying molecular mechanisms of Flotillins in breast cancer. Methods: Human adenocarcinoma MCF7 breast cancer cells were stably depleted of Flotillins by means of lentivirus mediated short hairpin RNAs. Western blotting, immunofluorescence and quantitative real-time PCR were used to analyze the expression of proteins of the epidermal growth factor receptor (EGFR) family. Western blotting was used to investigate the effect of EGFR stimulation or inhibition as well as phosphatidylinositol 3-kinase (PI3K) inhibition on mitogen activated protein kinase (MAPK) signaling. Rescue experiments were performed by stable transfection of RNA intereference resistant Flotillin proteins. Results: We here show that stable knockdown of Flotillin-1 in MCF7 cells resulted in upregulation of EGFR mRNA and protein expression and hyperactivation of MAPK signaling, whereas ErbB2 and ErbB3 expression were not affected. Treatment of the Flotillin knockdown cells with an EGFR inhibitor reduced the MAPK signaling, demonstrating that the increased EGFR expression and activity is the cause of the increased signaling. Stable ectopic expression of Flotillins in the knockdown cells reduced the increased EGFR expression, demonstrating a direct causal relationship between Flotillin-1 expression and EGFR amount. Furthermore, the upregulation of EGFR was dependent on the PI3K signaling pathway which is constitutively active in MCF7 cells, and PI3K inhibition resulted in reduced EGFR expression. Conclusions: This study demonstrates that Flotillins may not be suitable as cancer therapy targets in cells that carry certain other oncogenic mutations such as PI3K activating mutations, as unexpected effects are prone to emerge upon Flotillin knockdown which may even facilitate cancer cell growth and proliferation.

  • hetero oligomerization of reggie 1 Flotillin 2 and reggie 2 Flotillin 1 is required for their endocytosis
    Cellular Signalling, 2009
    Co-Authors: Tanja Babuke, Melanie Meister, Monia Amaddii, Mika O Ruonala, Christina Genzler, Alessandro Esposito, Ritva Tikkanen
    Abstract:

    Reggie-1/Flotillin-2 and reggie-2/Flotillin-1 are membrane raft associated proteins which have been implicated in growth factor signaling, phagocytosis, regulation of actin cytoskeleton and membrane trafficking. Membrane and raft association of reggies is mediated by myristoylation, palmitoylation and oligomerization. We have shown that upon EGF stimulation of cells, reggie-1 is tyrosine phosphorylated by Src kinase and endocytosed into late endosomes. Here we have analyzed the mechanism of the EGF-stimulated endocytosis of reggies in more detail and show that the Src-mediated phosphorylation of reggie-1 is not the driving force for endocytosis. However, hetero-oligomerization with reggie-2 is necessary for the translocation of reggie-1, which does not take place in the absence of reggie-2. In addition, the Y163F mutant of reggie-1, which is not capable of undergoing endocytosis, oligomerizes poorly with reggie-2. EGF stimulation results in changes in the size but not in the stoichiometry of the reggie hetero-oligomers, and reggie-1 oligomer size is decreased by knockdown of reggie-2. Based on our findings, we propose a model according to which reggie hetero-oligomers are dynamic, and changes in the size of the hetero-oligomers result in endocytosis of the complex from the plasma membrane.

  • role of egf induced tyrosine phosphorylation of reggie 1 Flotillin 2 in cell spreading and signaling to the actin cytoskeleton
    Journal of Cell Science, 2007
    Co-Authors: Carolin Neumanngiesen, Monia Amaddii, Inga Fernow, Ritva Tikkanen
    Abstract:

    Cholesterol and sphingolipid-rich membrane microdomains or rafts have been shown to be involved in signaling through many growth factor receptors but the molecular details of these processes are not well understood. The reggie/Flotillin proteins are ubiquitously expressed proteins with a poorly characterized function. They are constitutively associated with membrane rafts by means of acylation and oligomerization. Previous studies have implicated reggies in signaling, regulation of actin cytoskeleton and in membrane transport processes. In this study, we analyzed the putative role of reggie-1/Flotillin-2 in signaling through the epidermal growth factor receptor. We show that reggie-1 becomes phosphorylated by Src kinase at several tyrosines upon stimulation of cells with epidermal growth factor. In addition, Src and reggie-1 are present as a molecular complex. Epidermal growth factor stimulation of cells results in a Tyr163-dependent translocation of reggie-1 from the plasma membrane into endosomes. We also show that reggie-1 is capable of enhancing the spreading of cells, again in a tyrosine-dependent manner, and knockdown of reggie-1 interferes with spreading. Thus, we reveal a new function for reggie-1 in the regulation of cell adhesion and actin dynamics and in growth factor signaling.

  • a polycystin multiprotein complex constitutes a cholesterol containing signalling microdomain in human kidney epithelia
    Biochemical Journal, 2005
    Co-Authors: Tamara Roitbak, Ritva Tikkanen, Zurab Surviladze, Angela Wandingerness
    Abstract:

    Polycystins are plasma membrane proteins that are expressed in kidney epithelial cells and associated with the progression of ADPKD (autosomal dominant polycystic kidney disease). A polycystin multiprotein complex, including adherens junction proteins, is thought to play an important role in cell polarity and differentiation. Sucrose gradient analyses and immunoprecipitation studies of primary human kidney epithelial cells showed the polycystins and their associated proteins E-cadherin and β-catenin distributed in a complex with the raft marker Flotillin-2, but not caveolin-1, in high-density gradient fractions. The integrity of the polycystin multiprotein complex was sensitive to cholesterol depletion, as shown by cyclodextrin treatment of immunoprecipitated complexes. The overexpressed C-terminus of polycystin-1 retained the ability to associate with Flotillin-2. Flotillin-2 was found to contain CRAC (cholesterol recognition/interaction amino acid) cholesterol-binding domains and to promote plasma membrane cholesterol recruitment. Based on co-association of signalling molecules, such as Src kinases and phosphatases, we propose that the polycystin multiprotein complex is embedded in a cholesterol-containing signalling microdomain specified by Flotillin-2, which is distinct from classical light-buoyant-density, detergent-resistant domains.

I B Zborovskaya - One of the best experts on this subject based on the ideXlab platform.

  • simultaneous expression of Flotillin 1 Flotillin 2 stomatin and caveolin 1 in non small cell lung cancer and soft tissue sarcomas
    BMC Cancer, 2014
    Co-Authors: Ksenia Arkhipova, Anastasia N Sheyderman, K K Laktionov, Valeria V Mochalnikova, I B Zborovskaya
    Abstract:

    Background At the present time, there is a lack of data about the involvement of Flotillins and stomatin in the development of non-small cell lung cancer (NSCLC) and soft tissue sarcomas (STS). Moreover, changes in expression of members of different families of the microdomain-forming proteins (caveolins and SPFH-domain containing family) are usually investigated independently of each other. In this study we performed a combined analysis of Flotillins, stomatin, and caveolin-1 expression in these pathologies and evaluated correlations between generated data and clinicopathological characteristics of the specimens.

  • simultaneous expression of Flotillin 1 Flotillin 2 stomatin and caveolin 1 in non small cell lung cancer and soft tissue sarcomas
    BMC Cancer, 2014
    Co-Authors: Ksenia Arkhipova, Anastasia N Sheyderman, K K Laktionov, Valeria V Mochalnikova, I B Zborovskaya
    Abstract:

    At the present time, there is a lack of data about the involvement of Flotillins and stomatin in the development of non-small cell lung cancer (NSCLC) and soft tissue sarcomas (STS). Moreover, changes in expression of members of different families of the microdomain-forming proteins (caveolins and SPFH-domain containing family) are usually investigated independently of each other. In this study we performed a combined analysis of Flotillins, stomatin, and caveolin-1 expression in these pathologies and evaluated correlations between generated data and clinicopathological characteristics of the specimens. The protein and mRNA expression was analyzed by Western blotting and real-time PCR, respectively, in tissue specimens of patients undergoing surgery for non-small cell lung cancer and soft tissue sarcomas. Association between expression of studied proteins and patient clinicopathological characteristics or outcome was evaluated. Stomatin protein expression was down-regulated in 80% of NSCLC samples and this decrease significantly associated with presence of lymph node metastases. Flotillin-2 protein expression was up-regulated in the majority of NSCLC samples whereas caveolin-1α expression was decreased. We revealed a strong correlation between STOM and FLOT-1 mRNA expression in both pathologies, although the gene expression changes were diverse. Our data demonstrate for the first time that expression of stomatin, a poorly studied microdomain-forming protein, significantly changes in human tumors, thus pointing to its importance in the progression of NSCLC. We also suggest the existence of some relationship between the expression of these proteins.

Ksenia Arkhipova - One of the best experts on this subject based on the ideXlab platform.

  • simultaneous expression of Flotillin 1 Flotillin 2 stomatin and caveolin 1 in non small cell lung cancer and soft tissue sarcomas
    BMC Cancer, 2014
    Co-Authors: Ksenia Arkhipova, Anastasia N Sheyderman, K K Laktionov, Valeria V Mochalnikova, I B Zborovskaya
    Abstract:

    Background At the present time, there is a lack of data about the involvement of Flotillins and stomatin in the development of non-small cell lung cancer (NSCLC) and soft tissue sarcomas (STS). Moreover, changes in expression of members of different families of the microdomain-forming proteins (caveolins and SPFH-domain containing family) are usually investigated independently of each other. In this study we performed a combined analysis of Flotillins, stomatin, and caveolin-1 expression in these pathologies and evaluated correlations between generated data and clinicopathological characteristics of the specimens.

  • simultaneous expression of Flotillin 1 Flotillin 2 stomatin and caveolin 1 in non small cell lung cancer and soft tissue sarcomas
    BMC Cancer, 2014
    Co-Authors: Ksenia Arkhipova, Anastasia N Sheyderman, K K Laktionov, Valeria V Mochalnikova, I B Zborovskaya
    Abstract:

    At the present time, there is a lack of data about the involvement of Flotillins and stomatin in the development of non-small cell lung cancer (NSCLC) and soft tissue sarcomas (STS). Moreover, changes in expression of members of different families of the microdomain-forming proteins (caveolins and SPFH-domain containing family) are usually investigated independently of each other. In this study we performed a combined analysis of Flotillins, stomatin, and caveolin-1 expression in these pathologies and evaluated correlations between generated data and clinicopathological characteristics of the specimens. The protein and mRNA expression was analyzed by Western blotting and real-time PCR, respectively, in tissue specimens of patients undergoing surgery for non-small cell lung cancer and soft tissue sarcomas. Association between expression of studied proteins and patient clinicopathological characteristics or outcome was evaluated. Stomatin protein expression was down-regulated in 80% of NSCLC samples and this decrease significantly associated with presence of lymph node metastases. Flotillin-2 protein expression was up-regulated in the majority of NSCLC samples whereas caveolin-1α expression was decreased. We revealed a strong correlation between STOM and FLOT-1 mRNA expression in both pathologies, although the gene expression changes were diverse. Our data demonstrate for the first time that expression of stomatin, a poorly studied microdomain-forming protein, significantly changes in human tumors, thus pointing to its importance in the progression of NSCLC. We also suggest the existence of some relationship between the expression of these proteins.

Mathias Buttmann - One of the best experts on this subject based on the ideXlab platform.

  • identification of the Flotillin 1 2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis
    Journal of Neuroinflammation, 2017
    Co-Authors: S Hahn, G Trendelenburg, Madeleine Scharf, Y Denno, S Brakopp, Bianca Teegen, Christian Probst, Klauspeter Wandinger, Mathias Buttmann
    Abstract:

    Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against Flotillin in patients with multiple sclerosis (MS). The target antigen was identified by histo-immunoprecipitation using the patients’ sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and Flotillin-2 were identified as target autoantigens. They also reacted with recombinant human Flotillin-1/2 co-expressed in HEK293 cells, but not with the individual Flotillins in fixed- and live-cell assays. Moreover, neutralization using Flotillin-1/2, but not the single Flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-Flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-Flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. Autoantibodies against the Flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1–2% of patients with bona fide MS.

  • Identification of the Flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis
    'Springer Science and Business Media LLC', 2017
    Co-Authors: S Hahn, G Trendelenburg, Madeleine Scharf, Y Denno, S Brakopp, Bianca Teegen, Christian Probst, Klauspeter Wandinger, Mathias Buttmann, A. Haarmann
    Abstract:

    Abstract Background Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against Flotillin in patients with multiple sclerosis (MS). Methods The target antigen was identified by histo-immunoprecipitation using the patients’ sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. Results Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and Flotillin-2 were identified as target autoantigens. They also reacted with recombinant human Flotillin-1/2 co-expressed in HEK293 cells, but not with the individual Flotillins in fixed- and live-cell assays. Moreover, neutralization using Flotillin-1/2, but not the single Flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-Flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-Flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. Conclusions Autoantibodies against the Flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1–2% of patients with bona fide MS