Exosome Biogenesis: Role of Exosomal Cargo in the Production and Secretion of Exosomes



November 18, 2013

The molecular information content of exosomes is fundamental to their function. Exosomes, carry cell-type specific cargo targeted for extracellular destinations. While a constitutive synthesis of exosomes is conceivable as part of the cellular basis of tissue homeostasis we assume that the production of exosomes containing cell type-specific gene products may not be random but dictated by tissue physiology and cellular function; exosomes may be assembled and secreted in response to instructions received from the neighboring cells or from distant tissues. Thus an efficient way of coordinating the process of exosome production and secretion, which is temporally precise and functionally relevant, is to have the cell-type specific cargo a role in their biogenesis. We have used the human retinal pigment epithelium (RPE) as the functioning paradigm. RPE straddles the blood/retina barrier and physically and physiologically supports retinal photoreceptor function. Working with aB-crystallin (aB), a small heat shock and cell-type specific exosomal protein associated with a number of neuro-degenerations including Alzheimer’s, Parkinson’s disease, Multiple sclerosis and AMD (age-related macular degeneration), we demonstrate that this protein is essential for exosome biogenesis in the human RPE cells in culture. aB is found only in some cell types (for example most epithelial cells contain aB while most fibroblastic cell lines do not). Its presence in exosomes, therefore, allows us to address the question if the exosomal cargo has a role in exosome biogenesis? Understanding cell-type specific control of exosome biogenesis may allow us engineer exosomal content biologically. We will discuss our recent data obtained from these investigations.

Drug DiscoveryGenomicsInformatics

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