Ionita Ghiran,
,
Harvard Medical School/Beth Israel Deaconess Medical Center
Terminal Complement Components are Critical in the Release of Cellular RNA in Circulation
Tuesday, 21 March 2017 at 18:30
Add to Calendar ▼2017-03-21 18:30:002017-03-21 19:30:00Europe/LondonTerminal Complement Components are Critical in the Release of Cellular RNA in CirculationSELECTBIOenquiries@selectbiosciences.com
Despite of over 10 years of intense research, the intimate mechanisms
responsible for extracellular vesicles (EVs) formation (exosomes and
microvesicles), and the release of cellular RNA species (exRNAs) in
circulation are currently known. The complement system is comprised of
over 20 soluble and membrane bound proteins with critical roles in
recognizing, binding, and removal of foreign particles as well as
initiating and regulating innate and acquired immune responses.
Activation of the complement system occurs during both, normal
(circadian variation), and pathological conditions through either
classical, alternative, or lectine pathways leading to the formation and
transient insertion of C5b-9/Mac pore complex into cellular plasma
membrane. We hypothesis that a) MAC-insertion promotes a sudden,
significant and transient water and Ca++ influx, leading to: i)
endocytosis of the affected area, followed by delivery of
C5b-9/MAC-containing plasma membrane into the multi vesicular body
(MVB), and its incorporation into exosomes, or ii) exocytosis of the C9
channle/MAC-affected plasma membrane patch followed by microvesicles
(MVs) formation. In addition, the size of the MAC/C5b-9 pore, 12 nm, is
large enough to: i) allow cytoplasmic RNA species to be transferred into
the MVB following endocytosis of C5b-9/MAC-containing plasma membrane,
and ii) RNA species located near the plasma membrane to be released in
the extracellular space upon C5b-9/MAC insertion. Our results, for the
first time implicate MAC/C5b-9 as: i) a possible channel responsible for
exosomes and microparticle biogenesis, and ii) loading of cytosolic
RNAs into the exosomes, and iii) the direct release of cytoplasmic RNA
species into the circulation (exRNAs).
Add to Calendar ▼2017-03-20 00:00:002017-03-21 00:00:00Europe/LondonCirculating Biomarkers: Cell-Free Nucleic Acids, Proteins and Rare Circulating CellsSELECTBIOenquiries@selectbiosciences.com