Membrane phospholipid redistribution in cancer micro-particles and implications in the recruitment of cationic protein factors
| Autor: | Doris Grillo, Carol L. Williams, Igal Szleifer, Ming Zhao, J. Andrew Wasserstrom, Songwang Hou |
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| Rok vydání: | 2013 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities phosphatidylserine Histology RHOA Phospholipid GTPase Green fluorescent protein chemistry.chemical_compound phosphatidylethanolamine phosphatidylserine membrane asymmetry microparticles Rho GTPase Original Research Article lcsh:QH573-671 Lipid bilayer skin and connective tissue diseases Phosphatidylethanolamine biology lcsh:Cytology micro-particles Rho GTPase nutritional and metabolic diseases Cell Biology Phosphatidylserine membrane asymmetry Membrane chemistry Biochemistry phosphatidylethanolamine Biophysics biology.protein |
| Zdroj: | Journal of Extracellular Vesicles Journal of Extracellular Vesicles, Vol 3, Iss 0, Pp 1-10 (2014) Journal of Extracellular Vesicles; Vol 3 (2014) incl supplements |
| ISSN: | 2001-3078 |
| Popis: | Cancer cell-derived micro-particles (MPs) play important regulatory roles on cellular and system levels. These activities are attributed in part to protein factors carried by MPs. However, recruitment strategies for sequestering certain protein factors in MPs are poorly understood. In the current study, using exogenous and endogenously expressed phospholipid-binding probes, we investigated the distribution of membrane phospholipids in MPs as a potential mechanism for electrostatically enriching cationic protein factors in MPs. We detected a significant level of externalised phosphatidylethanolamine (PE) at the outer surface of MPs. This was accompanied, in the inner leaflet of the MP membrane, by a greater density of negatively charged phospholipids, particularly phosphatidylserine (PS). The local enrichment of PS in the inner surface of MPs was correlated with an elevated presence of small GTPases in a polybasic region (PBR)-dependent fashion. By employing a series of RhoA derivatives, including constitutively active and RhoA derivatives lacking a PBR, we could demonstrate that the congregation of RhoA in MPs was dependent on the presence of the PBR. A chimer with the fusion of PBR sequence alone to GFP significantly enhanced GFP localisation in MPs, indicative of a positive contribution of electrostatic interactions in RhoA recruitment to MPs. Using in silico thermodynamic simulations, we characterised the electrostatic interactions between PBR and anionic lipid membrane surface. In summary, the redistribution of membrane phospholipids in MPs has an impact on the local ionic density, and is likely a contributing factor in the electrostatic recruitment of membrane-associated proteins to MPs in a PBR-dependent fashion. Keywords: phosphatidylethanolamine; phosphatidylserine; membrane asymmetry; micro-particles; Rho GTPase (Published: 11 June 2014) Citation: Journal of Extracellular Vesicles 2014, 3 : 22653 - http://dx.doi.org/10.3402/jev.v3.22653 To access the supplementary material to this article, please see Supplementary files under Article Tools online. |
| Databáze: | OpenAIRE |
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