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Membrane remodelling by a lipidated endosomal sorting complex required for transport-III chimera, in vitro.

ABSTRACT: The complexity of eukaryotic cells is underscored by the compartmentalization of chemical signals by phospholipid membranes. A grand challenge of synthetic biology is building life from the 'bottom-up', for the purpose of generating systems simple enough to precisely interrogate biological pathways or for adapting biology to perform entirely novel functions. Achieving compartmentalization of chemistries in an addressable manner is a task exquisitely refined by nature and embodied in a unique membrane remodelling machinery that pushes membranes away from the cytosol, the ESCRT-III (endosomal sorting complex required for transport-III) complex. Here, we show efforts to engineer a single ESCRT-III protein merging functional features from its different components. The activity of such a designed ESCRT-III is shown by its ability to drive the formation of compartments encapsulating fluorescent cargo. It appears that the modular nature of ESCRT-III allows its functional repurposing into a minimal machinery that performs sophisticated membrane remodelling, therefore enabling its use to create eukaryotic-like multi-compartment architectures.

SUBMITTER: Marklew CJ

PROVIDER: S-EPMC6227774 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Membrane remodelling by a lipidated endosomal sorting complex required for transport-III chimera, <i>in vitro</i>.

Marklew C J CJ Booth A A Beales P A PA Ciani B B

Interface focus 20180817 5

The complexity of eukaryotic cells is underscored by the compartmentalization of chemical signals by phospholipid membranes. A grand challenge of synthetic biology is building life from the 'bottom-up', for the purpose of generating systems simple enough to precisely interrogate biological pathways or for adapting biology to perform entirely novel functions. Achieving compartmentalization of chemistries in an addressable manner is a task exquisitely refined by nature and embodied in a unique mem ...[more]

PMID: 30443329

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Project description:BackgroundThe genes involved in the endosomal sorting required for transport complex (ESCRT)-III pathway is a protective mechanism that delays cell death by repairing damaged plasma membranes. We aimed to evaluate if targeting ESCRT-III genes may be used as biomarkers for predicting the clinical outcomes of endometrial carcinoma (EC).MethodsTranscriptome RNA sequence (RNA-seq) data and genomic information of EC samples were obtained from The Cancer Genome Atlas (TCGA). The expression level, pathological relationship, pathway alterations, mutation, functional enrichment, associations with tumor infiltrating lymphocytes (TILs), and survival information of ESCRT-III genes including charged multivesicular body protein 2A (CHMP2A), CHMP2B, CHMP3, CHMP4B, CHMP4C, CHMP5, CHMP5, and CHMP7 in EC and normal tissues were explored through multiple datasets analysis.ResultsOur study demonstrated that CHMP2B, CHMP3, CHMP4B, CHMP5, CHMP5, and CHMP7 were significantly lower, whereas CHMP2A and CHMP4C were significantly higher in EC tissue than in normal tissue. All ESCRT pathway genes were significantly differentially expressed between tumor grades 2 and 3 and were positively correlated with each other. Except for CHMP5, the other seven ESCRT pathway genes were the most frequently mutated genes in the EC samples among all cancer types. Moreover, CHMP2A and CHMP7 had better prognostic potential in EC. CHMP2A, CHMP4B, and CHMP7 were significantly correlated with all four molecular subtypes in TCGA. Increased expression of CHMP2A and CHMP7 and decreased expression of CHMP4B were observed in EC samples than in serous carcinoma type samples. Furthermore, they were associated with tumor stages 1 and 2 and good survival outcomes for EC. Functional analysis revealed that the ESCRT-III genes were involved in the biological process (BP) of the membrane budding and multivesicular body (MVB) pathway; CHMP2A and CHMP7 participated in the ESCRT and ESCRT III complex disassembly, while CHMP5 was involved in ESCRT and ESCRT III complex assembly.ConclusionsMutations in CHMP2A and CHMP7 correspond to a better prognostic potential in EC. Upregulation of CHMP2A and CHMP7 and downregulation of CHMP4B are good prognostic indicators of the histological type, early tumor grade, and promising survival markers, thus becoming potential biomarkers and therapeutic targets for EC.

Dataset Information

Membrane remodelling by a lipidated endosomal sorting complex required for transport-III chimera, in vitro.

Publications

Membrane remodelling by a lipidated endosomal sorting complex required for transport-III chimera, <i>in vitro</i>.

Similar Datasets

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