Abstract
Exosomes and microvesicles (EMVs) are lipid bilayer-enclosed structures released from cells and participate in cell-to-cell communication via transport of biological molecules. EMVs play important roles in various pathologies, including cancer and neurodegeneration. The regulation of EMV biogenesis is thus of great importance and novel ways for manipulating their release from cells have recently been highlighted. One of the pathways involved in EMV shedding is driven by peptidylarginine deiminase (PAD) mediated post-translational protein deimination, which is calcium-dependent and affects cytoskeletal rearrangement amongst other things. Increased PAD expression is observed in various cancers and neurodegeneration and may contribute to increased EMV shedding and disease progression. Here, we review the roles of PADs and EMVs in cancer and neurodegeneration.
Highlights
Exosomes and microvesicles (EMVs) play physiological roles as mediators of intercellular communication, transferring molecules characteristic of their parental cells such as receptors, enzymes, cytokines, growth factors, and genetic material—including miRNAs—to recipient cells affecting diverse processes such as differentiation, migration, and angiogenesis [1,2,3,4]
One of the pathways involved in EMV shedding is driven by peptidylarginine deiminase (PAD) mediated post-translational protein deimination, which is calcium-dependent and affects cytoskeletal rearrangement amongst other things
Increased PAD expression is observed in various cancers and neurodegeneration and may contribute to increased EMV shedding and disease progression
Summary
Exosomes and microvesicles (EMVs) play physiological roles as mediators of intercellular communication, transferring molecules characteristic of their parental cells such as receptors, enzymes, cytokines, growth factors, and genetic material—including miRNAs—to recipient cells affecting diverse processes such as differentiation, migration, and angiogenesis [1,2,3,4]. Microvesicles (MVs), are 100–1000 nm sized phospholipid-rich vesicles that are released from the cell membrane of diverse cell types as part of normal cell physiology [10,11] and upon stimulation, with for example growth factors or cytokines, and/or in early apoptosis or [5,7]. Cellular components crucial for exosome formation include components of ESCRT, which are involved in the formation of multivesicular bodies (MVBs) and intraluminal vesicles [18,19]; syntetin and syndecan [20]; sphingolipid ceramide and tetraspanins [21]. Pharmacological PAD-inhibition has shown promising results in cancer models both in vitro [45,46] and in vivo [43,47], as well as in animal models of various autoimmune diseases [48,49,50,51,52], neuronal injury [53], hypoxia [54], and atherosclerosis [55]
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