Abstract
Transfer of cellular material via tunneling nanotubes (TNT) was recently discovered as a novel mechanism for intercellular communication. The role of intercellular exchange in communication of renal epithelium is not known. Here we report extensive spontaneous intercellular exchange of cargo vesicles and organelles between primary human proximal tubular epithelial cells (RPTEC). Cells were labeled with two different quantum dot nanocrystals (Qtracker 605 or 525) and intercellular exchange was quantified by high-throughput fluorescence imaging and FACS analysis. In co-culture, a substantial fraction of cells (67.5%) contained both dyes indicating high levels of spontaneous intercellular exchange in RPTEC. The double positive cells could be divided into three categories based on the preponderance of 605 Qtracker (46.30%), 525 Qtracker (48.3%) and approximately equal content of both Qtrackers (4.57%). The transfer of mitochondria between RPTECs was also detected using an organelle specific dye. Inhibition of TNT genesis by actin polymerization inhibitor (Latrunculin B) markedly reduced intercellular exchange (>60%) suggesting that intercellular exchange in RPTEC was in part mediated via TNT-like structures. In contrast, induction of cellular stress by Zeocin treatment increased tube-genesis in RPTEC. Our data indicates an unexpected dynamic of intercellular communication between RPTEC by exchange of cytosolic material, which may play an important role in renal physiology.
Highlights
Intercellular communication is a key process in the development and maintenance of multicellular organisms
Identification of tunneling nanotubes (TNT)-like structures in epithelial cells Using light microscopy, thin membranous structures bridging two or more cells were detected in human renal proximal tubular epithelial cells (RPTEC) and human mammary epithelial cells (HMEC) (Figure 1)
We report here the discovery of an unexpectedly high degree of spontaneous intercellular exchange between primary human kidney epithelial cells
Summary
Intercellular communication is a key process in the development and maintenance of multicellular organisms. A novel mechanism for intercellular communication was discovered by which nanotubular structures, consisting of thin membrane bridges, mediate membrane continuity between mammalian cells [1]. These channels, referred to as tunneling nanotubes (TNT), were shown to actively traffic cytosolic content from cell to cell within the interior of their filaments [1]. The emergence of the first in-vivo evidence for TNT-connectivity between immune cells of the corneal stroma suggest a central role for TNT-based intercellular communication in physiological processes of multi-cellular organism [8]
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