Interaction between microfilament and microtubule- dependent tensions and ischemia/hypoxic-induced alteration of structural tension in neuronal cells.

Intracellular mechanical tension plays a vital role in maintaining neuronal function and is generated steerablely by motor proteins along microfilaments (MFs) and microtubules (MTs). To explore the interaction between these subcellular tensions and elucidate their underlying mechanisms, we constructed MF- and MT-dependent tension probes using the Förster resonance energy transfer technique. Hypotonic stress activated MF and MT tensions in calcium-dependent manner, which antagonized outward expansion of cells synergistically; conversely, hypertonic stress attenuated MF and MT tensions in a calcium-independent manner and their interaction is antagonistical. In response to ischemia/hypoxia-related factors, glutamic acid upregulated MF and MT tensions synergistically, similarly to calcium signaling. Energy depletion elicited by ammonium ions increased MT tension, but not MF tension. Oxygen free radical stimulus had no effect on MT and MT tensions. However, MT tension was involved in the antagonism of MF tension in response to energy depletion and oxygen free radicals. Our findings suggest that intracellular MF and MT tensions can interact synergistically or antagonistically in neuronal cells, which is indispensable in ischemia/hypoxia -induced neuron dysfunction.