Dataset Information

Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.

ABSTRACT: Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of known and novel protein assemblies. We report the characterization of a previously undescribed endosome sorting complex that contains two well-conserved proteins with four predicted membrane-spanning domains. Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the TGN as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles within the MVB. Our results suggest the Vps55/68 complex mediates a novel, conserved step in the endosomal maturation process.

SUBMITTER: Schluter C

PROVIDER: S-EPMC2291407 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.

Schluter Cayetana C Lam Karen K Y KK Brumm Jochen J Wu Bella W BW Saunders Matthew M Stevens Tom H TH Bryan Jennifer J Conibear Elizabeth E

Molecular biology of the cell 20080123 4

Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of k ...[more]

PMID: 18216282

Similar Datasets

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

Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.

Publications

Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets