Mutations in the human VPS13 genes are responsible for neurodevelopmental and neurodegenerative disorders including chorea acanthocytosis (VPS13A) and Parkinson's disease (VPS13C). The mechanisms of these diseases are unknown. Genetic studies in yeast hinted that Vps13 may have a role in lipid exchange between organelles. In this study, we show that the N-terminal portion of VPS13 is tubular, with a hydrophobic cavity that can solubilize and transport glycerolipids between membranes. We also show that human VPS13A and VPS13C bind to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes (VPS13C), and to lipid droplets (both VPS13A and VPS13C). These findings identify VPS13 as a lipid transporter between the ER and other organelles, implicating defects in membrane lipid homeostasis in neurological disorders resulting from their mutations. Sequence and secondary structure similarity between the N-terminal portions of Vps13 and other proteins such as the autophagy protein ATG2 suggest lipid transport roles for these proteins as well.
Tethering factors have been shown to interact with Rabs and SNAREs and, more recently, with coat proteins. Coat proteins are required for cargo selection and membrane deformation to bud a transport vesicle from a donor compartment. It was once thought that a vesicle must uncoat before it recognizes its target membrane. However, recent findings have revealed a role for the coat in directing a vesicle to its correct intracellular destination. In this review we will discuss the literature that links coat proteins to vesicle targeting events.
The reovirus core is an assembly with a relative molecular mass of 52 million that synthesizes, modifies and exports viral messenger RNA. Analysis of its structure by X-ray crystallography shows that there are alternative, specific and completely non-equivalent contacts made by several surfaces of two of its proteins; that the RNA capping and export apparatus is a hollow cylinder, which probably sequesters its substrate to ensure completion of the capping reactions; that the genomic double-stranded RNA is coiled into concentric layers within the particle; and that there is a protein shell that appears to be common to all groups of double-stranded RNA viruses.
Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably measure and analyze them with the hope of ultimately facilitating knowledge production and dissemination within and outside the field of contact-site research.
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