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Reggiori, F.

Publications and source records attributed to Reggiori, F..

2 recordsLinked to original sources

Lecithin:Retinol Acyl Transferase (LRAT) inducesthe formation of lipid droplets

Lipid droplets are unique and nearly ubiquitous organelles that store neutral lipids in a hydrophobic core, surrounded by a monolayer of phospholipids. The primary neutral lipids are triacylglycerols and steryl esters. It is not known whether other classes of neutral lipids can form lipid droplets by themselves. Here we show that production of retinyl esters by lecithin:retinol acyl transferase (LRAT) in yeast cells, incapable of producing triacylglycerols and steryl esters, causes the formation of lipid droplets. By electron microscopy, these lipid droplets are morphologically indistinguishable from those in wild-type cells. In silico and in vitro experiments confirmed the propensity of retinyl esters to segregate from membranes and to form lipid droplets. The hydrophobic N-terminus of LRAT displays preferential interactions with retinyl esters in membranes and promotes the formation of large retinyl ester-containing lipid droplets in mammalian cells. Our combined data indicate that the molecular design of LRAT is optimally suited to allow the formation of characteristic large lipid droplets in retinyl ester-storing cells.

biochemistry

Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling

Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria employ lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection.\n\nHere, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, that extend beyond its role as an adhesion molecule. We found that LecB associates with several growth factor receptors and dampens their signalling pathways, leading to the arrest of cell cycle. Additionally, we describe a novel LecB-triggered mechanism to downregulate host cell receptors by showing that LecB leads to insulin-like growth factor receptor 1 internalisation, without receptor activation, and subsequent missorting towards intracellular endosomal compartments.\n\nOverall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.

cell biology