Regulatory mechanisms of nanovesicle secretion

Funded by: The Danish Council for Independent Research | Natural Sciences (FNU) (Project DFF – 4002-00364)

Summary: Extracellular nanovesicles called “exosomes” are small membrane-bound vesicles that are secreted by a variety of cell types. Exosomes contain various molecular constituents of their cell of origin, including proteins and genetic materials. The exosome release pathway contributes towards protein secretion, antigen presentation and pathogen transfer and roles of exosomes in intercellular communications and transfer of materials have been studied in immunology, neurobiology, stem cell and tumor biology. This project will study urinary exosomes to determine a basic mechanism for regulated exosome secretion and their role in cell:cell communication. 

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Objectives: This project will combine qualitative and quantitative mass spectrometry (MS) analyses of urinary exosomes and exosomes secreted from relevant kidney cell cultures with extensive bioinformatics, cell biological and biochemical studies to address the following questions:

1) Are proteins within urinary exosomes modified by specific post-translational modifications (ubiquitination)? Are these modifications present other types of exosomes and thus a basic mechanism for exosome formation and secretion?

2) Under certain conditions, can exosome secretion (or constituents) be modified or regulated?

3) What genetic information do urinary exosomes hold, and can this information (or proteins) from exosomes be transmitted between renal cells? Can exosomes transfer information via transcytosis?