The Metalloprotease Meprinβ Processes E-Cadherin and Weakens Intercellular Adhesion

BACKGROUND: Meprin (EC 3.4.24.18), an astacin-like metalloprotease, is expressed in the epithelium of the intestine and kidney tubules and has been related to cancer, but the mechanistic links are unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used MDCK and Caco-2 cells stably transfected with meprin alpha and or meprin beta to establish models of renal and intestinal epithelial cells expressing this protease at physiological levels. In both models E-cadherin was cleaved, producing a cell-associated 97-kDa E-cadherin fragment, which was enhanced upon activation of the meprin zymogen and reduced in the presence of a meprin inhibitor. The cleavage site was localized in the extracellular domain adjacent to the plasma membrane. In vitro assays with purified components showed that the 97-kDa fragment was specifically generated by meprin beta, but not by ADAM-10 or MMP-7. Concomitantly with E-cadherin cleavage and degradation of the E-cadherin cytoplasmic tail, the plaque proteins beta-catenin and plakoglobin were processed by an intracellular protease, whereas alpha-catenin, which does not bind directly to E-cadherin, remained intact. Using confocal microscopy, we observed a partial colocalization of meprin beta and E-cadherin at lateral membranes of incompletely polarized cells at preconfluent or early confluent stages. Meprin beta-expressing cells displayed a reduced strength of cell-cell contacts and a significantly lower tendency to form multicellular aggregates. CONCLUSIONS/SIGNIFICANCE: By identifying E-cadherin as a substrate for meprin beta in a cellular context, this study reveals a novel biological role of this protease in epithelial cells. Our results suggest a crucial role for meprin beta in the control of adhesiveness via cleavage of E-cadherin with potential implications in a wide range of biological processes including epithelial barrier function and cancer progression

Wavefront Velocity Oscillations of Carbon-Nanotube-Guided Thermopower Waves: Nanoscale Alternating Current Sources

The nonlinear coupling between exothermic chemical reactions and a nanowire or nanotube with large axial heat conduction results in a self-propagating thermal wave guided along the nanoconduit. The resulting reaction wave induces a concomitant thermopower wave of high power density (>7 kW/kg), resulting in an electrical current along the same direction. We develop the theory of such waves and analyze them experimentally, showing that for certain values of the chemical reaction kinetics and thermal parameters, oscillating wavefront velocities are possible. We demonstrate such oscillations experimentally using a cyclotrimethylene-trinitramine/multiwalled carbon nanotube system, which produces frequencies in the range of 400 to 5000 Hz. The propagation velocity oscillations and the frequency dispersion are well-described by Fourier's law with an Arrhenius source term accounting for reaction and a linear heat exchange with the nanotube scaffold. The frequencies are in agreement with oscillations in the voltage generated by the reaction. These thermopower oscillations may enable new types of nanoscale power and signal processing sources