Membrane Rafts in the Erythrocyte Membrane: A Novel Role of MPP1p55

Sikorski, Aleksander F.; Podkalicka, Joanna; Jones, Walis; Biernatowska, Agnieszka

doi:10.1007/978-3-319-11280-0_5

Cited by 8 publications

(7 citation statements)

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“…in [ 21 ]). Our recent studies demonstrated that a peripheral membrane protein, MPP1/p55 (membrane palmitoylated protein 1), takes part in the regulation of PM lateral organization of erythrocyte precursors (reviewed in [ 22 ]). MPP1, a MAGUK (membrane associated guanylate kinases) family protein, was originally described in erythrocytes as a skeletal protein that participates in the linking of the membrane skeleton elements to the PM by formation of a tripartite complex with protein 4.1 and glycophorin C [ 23 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras

et al. 2018

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Signaling complexes are localized to distinct plasma-membrane domains which undergo precise spatiotemporal regulation. A crucial link between membrane dynamics and the small GTPase, H-Ras, has been suggested, connecting membrane localization, clustering and scaffolding with its activity and signal transduction. Results of this study suggest a relationship between MPP1 and/or MPP1-dependent plasma-membrane organization and H-Ras activation. Namely, we show here that in HEL cells, MPP1 knock-down lead to the disruption of signaling cascade(s) from the activated insulin receptor. The signal inhibition occurred at the level of H-Ras, as it showed impaired GDP-to-GTP exchange and further interaction with its effector molecule, Raf. Moreover, in these cells H-Ras detergent-resistant membrane localization was not sensitive to insulin treatment which may imply molecular mechanism via which MPP1 affects functions of other proteins which may be connected with functional domain formation. Understanding the link between MPP1 and activation of H-Ras, may provide an important insight into the complexity of Ras related signaling pathways which may become a potential target for associated cancer therapies.

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Section: Introductionmentioning

confidence: 99%

The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras

et al. 2018

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“…Despite several years of research, there is no great progress towards answering this question. For example, as was mentioned previously [4] there have been several raft-dependent signaling pathways found in red blood cells, e.g. Gsa-protein coupled b-adrenergic receptors cAMP-kinase A leading to the phosphorylation of adducin [5,6].…”

Section: Introductionmentioning

confidence: 83%

“…The functional role of MPP1 palmitoylation is currently not well understood but it is believed that MPP1 palmitoylation is a crucial event involved in raft formation, which might be linked to pathology [4,28,61]. Studies performed on erythroid precursor cell line HEL cells revealed that following inhibition of palmitoylation by treatment with the potent protein acetyltransferase (PAT) inhibitor 2-BrP (2-bromo palmitate), the amount of DRM fraction was markedly decreased.…”

Section: Mpp1 Is Involved In Resting State Raft Formation In Erythroimentioning

confidence: 99%

“…The erythrocyte membrane bilayer is not homogeneous; it is characterized by relatively high cholesterol content (> 20% lipids by weight) and a set of lipids including sphingolipids (sphingomyelin (SM) and glycolipids) which participate in the generation of membrane lateral heterogeneity by forming domains among which lipid or membrane rafts have been attracting the attention of many laboratories. Literature up to 2014 was surveyed in the previous review [4]. The question remains whether membrane rafts are functional or just remnants of the early stages of nucleated cells.…”

Section: Introductionmentioning

confidence: 99%

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MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

Trybus

Niemiec

Biernatowska

et al. 2019

Folia Histochem Cytobiol.

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Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The wellknown function of this protein is to participate in formation of the junctional complex of the erythrocyte membrane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.

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“…Disruption of the structure of such domains by cholesterol depletion may lead to modification of signal transduction. We hypothesize that simvastatin may specifically disorganize membrane rafts and therefore disturb the EGFR-dependent signalling pathways which usually promote cell proliferation and metastasis in epithelial cancers [ 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Immunoliposomes with Simvastatin as a Potential Therapeutic in Treatment of Breast Cancer Cells Overexpressing HER2—An In Vitro Study

Matusewicz

Podkalicka

Sikorski

2018

Cancers

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Lipophilic statins are promising candidates for breast cancer treatment. However, anticancer therapy requires much higher doses of statins than can be delivered orally, and such high doses are known to exert more adverse effects. The main objective of our study was to design a targeted, therapeutic liposomal carrier of simvastatin characterised by high stability and specificity towards breast cancer cells. We chose SKBR3, the cell line that showed the highest sensitivity for simvastatin and liposomal simvastatin treatment. Additionally, SKBR3 has a notably high expression level of human epidermal growth factor receptor 2 (HER2), which we used as a target for our immunoliposomes. To do so we attached humanized anti-HER2 antibody to the envelope of liposomes. We tested the stability and selectivity of the proposed formulation along with the toxicity, ability to induce apoptosis and the effect on signalling pathways involving Akt and Erk kinases. The immunoliposomal formulation of simvastatin is characterized by long-term stability, high selectivity towards HER2-overexpressing breast cancer cells, low non-specific cytotoxicity and effective inhibition of the growth of target cells, presumably by inhibition of signalling pathways and induction of apoptosis. Hence, for the first time, we propose the use of immunoliposomes with simvastatin, targeted directly towards breast cancer cells overexpressing HER2. The prepared immunoliposomes may become a proof of concept in developing new anticancer therapy.

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Membrane Rafts in the Erythrocyte Membrane: A Novel Role of MPP1p55

Abstract: Abbreviations

Cited by 8 publications

References 98 publications

The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras

The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras

MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

Immunoliposomes with Simvastatin as a Potential Therapeutic in Treatment of Breast Cancer Cells Overexpressing HER2—An In Vitro Study

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