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Transporting disease related cargo in the cell

Retrograde transport, the shuttling of proteins and lipids between vesicles inside the cell and membrane systems is critical for a range of cell functions. Recent evidence has linked this process to diseases as diverse as Alzheimer's and hepatitis C.
Transporting disease related cargo in the cell
Formation of internal vesicles or endosomes in the cytoplasm – clathrin independent endocytosis – involves several cell surface proteins which are internalised. The EU-funded RETROMER (The mechanism of retrograde trafficking by retromer) project has investigated how cargo proteins are sorted, how membranes bend to form pits that become endosomes and the mechanism that initiates the whole process.

The researchers discovered that a carbohydrate-binding protein galectin-3 (Gal3) triggers formation of clathrin-independent carriers (CLICs). The process also requires glycosphingolipid (GSL) for clustering and membrane bending.

Gal3 reacts with a defined set of cargo proteins. Interestingly, analysis of different galectins revealed that each has its own profile and that there are different CLIC populations using the same mechanism.

RETROMER research on the role of Gal3 in retrograde trafficking has been published in Nature Cell Biology. The relationship between Gal3 and GSLs has been submitted to PLOS ONE for publication.

GSLs are preserved through evolution and are present in bacteria, fungi and plants through to all mammalian cell types. As cellular receptors for pathogens and pathogenic molecules, they are critical for cell adhesion, migration and signalling. Identification of how GSLs regulate these functions could lead to disease therapies involving membranes and trafficking of disease-related cargo molecules.

Related information

Keywords

Disease, cargo, retrograde transport, clathrin independent endocytosis, Gal3, GSL
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