The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles

• DOI: 10.1371/journal.pbio.2002354
• Publication Date: 2017-08-14T23:32:37Z
• Authors: Bing Xu; Ying Fu; Yan Liu; Sosse Agvanian; Robert C. Wirka; Rachel Baum; Kang Zhou; Robin M. Shaw; TingTing Hong
• Keywords: ESCRT; Microvesicle; Cardiac muscle

Microparticles (MPs) are cell–cell communication vesicles derived from the cell surface plasma membrane, although they not known to originate cardiac ventricular muscle. In cardiomyocytes, membrane deformation protein bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response stress calcium signaling apparatus. We explored possibility that cBIN1-microfolds externally released cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found mouse cBIN1 exists about 200 nm size, is consistent size of MPs. mice cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs plasma, supporting origin. Cardiac release was also evidenced by detection medium bathing a pure population isolated adult human osmotic shock increased enzyme-linked immunosorbent assay (ELISA), level decreased humans heart failure, condition reduced muscle cBIN1, both support MPs hearts. Exploring putative mechanisms MP release, fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body 4B (CHMP4B) colocalizes coimmunoprecipitates an interaction enhanced actin stabilization. HeLa cells overexpression, knockdown CHMP4B cBIN1-MPs. truncation mutants, N-terminal BAR (N-BAR) domain binding release. This study links superfamily ESCRT pathway biogenesis mammalian cells, identifying elements cytoplasmic into blood.