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Vol. 19, Issue 8, 3442-3453, August 2008

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Vacuole Membrane Protein 1 Is an Endoplasmic Reticulum Protein Required for Organelle Biogenesis, Protein Secretion, and Development

Javier Calvo-Garrido^*, Sergio Carilla-Latorre^*, Francisco Lázaro-Diéguez, Gustavo Egea, and Ricardo Escalante^*

*Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain; Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Institut de Nanociència i Nanotecnologia, Universitat de Barcelona, 08036 Barcelona, Spain

Submitted January 25, 2008; Revised May 22, 2008; Accepted June 4, 2008
Monitoring Editor: Francis A. Barr

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.

Address correspondence to: Ricardo Escalante (rescalante{at}iib.uam.es)

Abbreviations used: CV, contractile vacuole; ER, endoplasmic reticulum; GFP, green fluorescence protein; PDI, protein disulfide isomerase; VMP1, vacuole membrane protein 1; TEM, transmission electron microscopy.

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