Spatio-temporal MAPK dynamics mediate cell behavior coordination during fungal somatic cell fusion

Mitogen-activated protein kinases (MAPKs) are conserved regulators of proliferation, differentiation and adaptation in eukaryotic cells. Their activity often involves changes in their subcellular localization, indicating an important role for these spatio-temporal dynamics in signal transmission. A striking model illustrating these dynamics is somatic cell fusion in Neurospora crassa. Germinating spores of this fungus rapidly alternate between signal sending and receiving, thereby establishing a cell-cell dialog, which involves the alternating membrane recruitment of the MAPK MAK-2 in both fusion partners. Here, we show that the dynamic translocation of MAK-2 is essential for coordinating the behavior of the fusion partners before physical contact. The activation and function of the kinase strongly correlate with its subcellular localization, indicating a crucial contribution of the MAPK dynamics in establishing regulatory feedback loops, which establish the oscillatory signaling mode. In addition, we provide evidence that MAK-2 not only contributes to cell-cell communication, but also mediates cell-cell fusion. The MAK-2 dynamics significantly differ between these two processes, suggesting a role for the MAPK in switching of the cellular program between communication and fusion.