Yeast and other lower eukaryotic organisms for studies of Vps13 proteins in health and disease

Abstract Human Vps13 proteins are associated with several diseases, including the neurodegenerative disorder Chorea‐acanthocytosis (ChAc), yet the biology of these proteins is still poorly understood. Studies in Saccharomyces cerevisiae, Dictyostelium discoideum, Tetrahymena thermophila and Drosophila melanogaster point to the involvement of Vps13 in cytoskeleton organization, vesicular trafficking, autophagy, phagocytosis, endocytosis, proteostasis, sporulation and mitochondrial functioning. Recent findings show that yeast Vps13 binds to phosphatidylinositol lipids via four different regions and functions at membrane contact sites, enlarging the list of Vps13 functions. This review describes the great potential of simple eukaryotes to decipher disease mechanisms in higher organisms and highlights novel insights into the pathological role of Vps13 towards ChAc. Synopsis Vps13 proteins play a prominent role in human health and disease, yet their precise functions remain obscure. Studies using simple eukaryotes indicated their role in: the actin cytoskeleton; vesicular trafficking; regulation of membrane contact sites; mitochondrial functioning and autophagy. These studies allowed for the yeast Vps13 protein to be classified as a lipid‐binding protein. Furthermore, these studies revealed the pathogenic mechanism of the mutations found in the VPS13‐associated neurodegenerative disorder Chorea‐acanthocytosis. Recent findings are presented and discussed.
Source: Traffic - Category: Research Authors: Tags: REVIEW Source Type: research