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Published on: October 23, 2016
Vacuole membrane protein 1 is an endoplasmic reticulum protein required for organelle biogenesis, protein secretion,
Javier Calvo-Garrido1, Sergio Carilla-Latorre, Francisco Lázaro-Diéguez
1Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Abstract:
Vacuole membrane protein 1 (Vmp1) is membrane protein of unknown molecular function that has been associated with pancreatitis and cancer. The social amoeba Dictyostelium discoideum has a vmp1-related gene that we identified previously in a functional genomic study. Loss-of-function of this gene leads to a severe phenotype that compromises Dictyostelium growth and development. The expression of mammalian Vmp1 in a vmp1(-) Dictyostelium mutant complemented the phenotype, suggesting a functional conservation of the protein among evolutionarily distant species and highlights Dictyostelium as a valid experimental system to address the function of this gene. Dictyostelium Vmp1 is an endoplasmic reticulum protein necessary for the integrity of this organelle. Cells deficient in Vmp1 display pleiotropic defects in the secretory pathway and organelle biogenesis. The contractile vacuole, which is necessary to survive under hypoosmotic conditions, is not functional in the mutant. The structure of the Golgi apparatus, the function of the endocytic pathway and conventional protein secretion are also affected in these cells. Transmission electron microscopy of vmp1(-) cells showed the accumulation of autophagic features that suggests a role of Vmp1 in macroautophagy. In addition to these defects observed at the vegetative stage, the onset of multicellular development and early developmental gene expression are also compromised.
Insights
Vacuole membrane protein 1 (Vmp1) is crucial for cell organelle integrity and function. Dictyostelium Vmp1 deficiency causes severe defects in secretion, organelle biogenesis, and development, highlighting conserved functions.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Vacuole membrane protein 1 (Vmp1) is a membrane protein linked to pancreatitis and cancer, with its molecular function largely unknown.
- A Vmp1-related gene in Dictyostelium discoideum, when its function is lost, results in significant growth and developmental defects.
- Mammalian Vmp1 expression rescues the Dictyostelium mutant phenotype, indicating conserved function across species.
Purpose of the Study:
- To investigate the molecular function of Vmp1 using Dictyostelium discoideum as a model system.
- To elucidate the role of Vmp1 in cellular processes, including organelle integrity and the secretory pathway.
- To explore the involvement of Vmp1 in macroautophagy and multicellular development.
Main Methods:
- Functional genomic study in Dictyostelium discoideum.
- Complementation assays using mammalian Vmp1.
- Phenotypic analysis of vmp1-null mutants, including assessment of organelle structure and function.
- Transmission electron microscopy to examine cellular ultrastructure.
- Evaluation of developmental processes and gene expression.
Main Results:
- Dictyostelium Vmp1 is localized to the endoplasmic reticulum and is essential for its integrity.
- Vmp1 deficiency leads to pleiotropic defects in the secretory pathway, contractile vacuole function, Golgi apparatus structure, and endocytic pathway.
- Cells lacking Vmp1 exhibit accumulation of autophagic features, suggesting a role in macroautophagy.
- Vegetative growth and multicellular development, including early developmental gene expression, are impaired in vmp1-null mutants.
Conclusions:
- Dictyostelium Vmp1 plays a critical role in maintaining endoplasmic reticulum integrity and overall cellular function.
- The conserved function of Vmp1 highlights Dictyostelium as a valuable model for studying Vmp1's role in health and disease.
- Vmp1 is implicated in diverse cellular processes, including organelle biogenesis, macroautophagy, and developmental progression.
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