Resolving the two-body problem: A postulated role for the V0 sector of the V0V1-ATPase in exosome biogenesis and multivesicular body fate.

Because the discovery of the multivesicular body (MVB) as the origin of secreted vesicles or exosomes, the question arose and still looms-what distinguishes an MVB destined for fusion with the plasma membrane (EXO-MVB) facilitating exosome release from an MVB involved in transport of content to the lysosome (LYSO-MVB). Do they have independent origins? Hence, the two-body problem. We hypothesize that a key to this conundrum is the membrane spanning V0 sector of the proton pump, V0V1-ATPase.

Extracellular vesicles - on the cusp of a new language in the biological sciences.

Extracellular vesicles (EVs) play a key role both in physiological balance and homeostasis and in disease processes through their ability to participate in intercellular signaling and communication. An ever-expanding knowledge pool and a myriad of functional properties ascribed to EVs point to a new language of communication in biological systems that has opened a path for the discovery and implementation of novel diagnostic applications. EVs originate in the endosomal network and via non-random shedding from the plasma membrane by mechanisms that allow the packaging of functional cargoes, including proteins, lipids, and genetic materials.

The microenvironment-a general hypothesis on the homeostatic function of extracellular vesicles.

Extracellular vesicles (EVs), exosomes and microvesicles, is a burgeoning field of biological and biomedical research that may change our understanding of cell communication in plants and animals while holding great promise for the diagnosis of disease and the development of therapeutics. However, the challenge remains to develop a general hypothesis about the role of EVs in physiological homeostasis and pathobiology across kingdoms. While they can act systemically, EVs are often seen to operate locally within a microenvironment.

A brief history of nearly EV-erything - The rise and rise of extracellular vesicles.

Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes.

Extracellular vesicles and homeostasis-An emerging field in bioscience research.

To keep abreast of developments in the biological sciences and in parallel fields such as medical education, () has created a special collections category, special collections ( SC), that target, among other topics, emerging disciplines in the biomedical sciences. This SC is focused on the emerging field of extracellular vesicles (EVs) and homeostasis. Leading investigators in the biology of EVs around the globe have contributed to this collection of articles that cover the gamut of research activities from biogenesis and secretion to physiological function.

Extracellular Vesicles: Exosomes and Microvesicles, Integrators of Homeostasis.

Extracellular vesicles (EVs), cell-derived membrane structures, are secreted after fusion of endosomes with the plasma membrane (exosomes) or shed from the plasma membrane (microvesicles). EVs play a key role both in physiological balance and homeostasis and in disease processes by their ability to participate in intercellular signaling and communication.

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair.

Healthy repair of cutaneous injury is a coordinated response of inflammatory cells, secreted factors, and biologically active extracellular vesicles (EVs). Although constitutive release of EVs into biologic fluids is a hallmark of cultured cells and tumors, their payload and biologic activity appears to be tightly regulated. We show that Tre-2/Bub2/Cdc16 (TBC1) domain family member 3 (TBC1D3) drives the release of an EV population that causes a decrease in phosphorylation of the transcription factor signal transducer and activator of transcription 3 in naive recipient cells.

Exosomes and extracellular vesicles: the path forward.

Over the course of the past several decades, the concept that extracellular vesicles, exosomes and microvesicles, operate as cellular "housekeepers" and as agents for communication between and among cells and tissues, has emerged into one of the most promising yet vexing problems facing the biomedical community. Already, extracellular vesicles from biological fluids are being used for diagnostic purposes and hopes abound for their use as therapeutic agents. However, the most basic mechanistic questions surrounding their biogenesis and function in cellular and tissue homeostasis remain largely unexplored.

Technology gap assessment for a future large-aperture ultraviolet-optical-infrared space telescope.

The Advanced Technology Large Aperture Space Telescope (ATLAST) team identified five key technology areas to enable candidate architectures for a future large-aperture ultraviolet/optical/infrared (LUVOIR) space observatory envisioned by the NASA Astrophysics 30-year roadmap, "Enduring Quests, Daring Visions." The science goals of ATLAST address a broad range of astrophysical questions from early galaxy and star formation to the processes that contributed to the formation of life on Earth, combining general astrophysics with direct-imaging and spectroscopy of habitable exoplanets. The key technology areas are internal coronagraphs, starshades (or external occulters), ultra-stable large-aperture telescope systems, detectors, and mirror coatings.

Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers.

To correlate H2Bub1 expression with outcome in colorectal cancer, H2Bub1 expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinicopathological parameters.H2Bub1 IHC was seen in 1256 (79.

Extracellular vesicles shuffling intercellular messages: for good or for bad.

The release of extracellular vesicles (EVs) is a highly conserved process exploited by diverse organisms as a mode of intercellular communication. Vesicles of sizes ranging from 30 to 1000nm, or even larger, are generated by blebbing of the plasma membrane (microvesicles) or formed in multivesicular endosomes (MVEs) to be secreted by exocytosis as exosomes. Exosomes, microvesicles and other EVs contain membrane and cytosolic components that include proteins, lipids and RNAs, a composition that differs related to their site of biogenesis.

Loss of RNA-binding motif protein 3 expression is associated with right-sided localization and poor prognosis in colorectal cancer.

Aims: RNA-binding motif protein 3 (RBM3) has recently been suggested as a prognostic biomarker in an array of human cancers. This study aimed to examine its effects in colorectal cancers.

Methods And Results: RBM3 expression was analysed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers (CRCs).

EVpedia: a community web portal for extracellular vesicles research.

Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging.

Results: We present an improved version of EVpedia, a public database for EVs research.

Regulation of AMPK activation by CD36 links fatty acid uptake to β-oxidation.

Increases in muscle energy needs activate AMPK and induce sarcolemmal recruitment of the fatty acid (FA) translocase CD36. The resulting rises in FA uptake and FA oxidation are tightly correlated, suggesting coordinated regulation. We explored the possibility that membrane CD36 signaling might influence AMPK activation.

Rab5 isoforms orchestrate a "division of labor" in the endocytic network; Rab5C modulates Rac-mediated cell motility.

Rab5, the prototypical Rab GTPase and master regulator of the endocytic pathway, is encoded as three differentially expressed isoforms, Rab5A, Rab5B and Rab5C. Here, we examined the differential effects of Rab5 isoform silencing on cell motility and report that Rab5C, but neither Rab5A nor Rab5B, is selectively associated with the growth factor-activation of Rac1 and with enhanced cell motility. Initial observations revealed that silencing of Rab5C expression, but neither Rab5A nor Rab5C, led to spindle-shaped cells that displayed reduced formation of membrane ruffles.

Regulation of Rab5 function during phagocytosis of live Pseudomonas aeruginosa in macrophages.

Pseudomonas aeruginosa, a Gram-negative opportunistic human pathogen, is a frequent cause of severe hospital-acquired infections. Effectors produced by the type III secretion system disrupt mammalian cell membrane trafficking and signaling and are integral to the establishment of P. aeruginosa infection.

Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is regulated by protein palmitoylation.

Expression of the hominoid-specific oncoprotein TBC1D3 promotes enhanced cell growth and proliferation by increased activation of signal transduction through several growth factors. Recently we documented the role of CUL7 E3 ligase in growth factors-induced ubiquitination and degradation of TBC1D3. Here we expanded our study to discover additional molecular mechanisms that control TBC1D3 protein turnover.