The Vps (vacuolar protein sorting) group of proteins was identified in yeast Saccharomyces cerevisiae. Among the Vps proteins, there is the VPS13 family, proteins of which are present in organisms from different systematic groups. In yeast there is only one VPS13 protein, while in humans there are four VPS13 family members - hVPS13A-D. These are large proteins of characteristic domain structure. Mutations in hVPS13 genes are linked to rare neurodegenerative disorders: chorea- acanthocytosis (hVPS13A), Cohen syndrome (hVPS13B), predispose to early onset into Parkinson disease (hVPS13C) and lead to ataxia/spastic paraplegia (hVPS13D). Lack of clear diagnostic criteria and broad spectrum of nonspecific symptoms cause the misdiagnosis of several patients with neurodegeneration and it is difficult to estimate the number of individuals with mutations in hVPS13 genes. The importance of VPS13 family proteins for human health turns interest of research on finding VPS13 protein function, which remains unknown. The research is mostly performed on several experimental models in which deficit of those proteins was acquired by deletions or gene expression silencing, or on cells from patients. Several changes were found in cells lacking VPS13 proteins on cellular level, such as changes in intracellular protein trafficking between Golgi apparatus, plasma membrane and endosomes, changes in mitochondria functioning and changes in organization of cytoskeletons, mainly actin cytoskeleton. However, it is unknown which alterations are primary and which secondary, compensatory. Recently research done on yeast revealed that VPS13 is a protein of the membrane contact sites, the structures involved in exchange of metabolites between different organelles. Such localization seems to be essential for VPS13 function. Based on literature we propose a hypothesis that VPS13 might actively participate in exchange of the lipids between membranes of organelles in membrane contact sites what could explain most of the phenotypes caused by lack of VPS13 protein.

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Journal Article | Review

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Kamińska J, Kolakowski D

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