The Ca2+-binding protein CSE links Ca2+-signaling with cell-cell communication in multicellular cyanobacteria

Abstract/SummaryBecause of their multicellular lifestyle, filamentous cyanobacteria have evolved sophisticated cell-cell communication machinery to exchange, synchronize, and coordinate the efforts of individual cells in the filament. Analogous to gap junctions that were regarded as a purely Eukaryotic feature, multicellular cyanobacteria were found also to coordinate their cell-cell communication via septal junctions (SJs). However, the molecular signals that regulate the cell-cell communication machinery and SJs assembly are largely unknown. Lately, Ca2+- signaling has been implicated in regulating cell junctions in neurons. We recently discovered a new Ca2+-sensor protein, CSE, exclusively found in multicellular cyanobacteria. Here, we investigated CSE as a potential link between intracellular Ca2+-signaling and cell-cell communication. We solved the solution NMR structure of CSE in its Ca2+-bound state and revealed that CSE acts as Ca2+-buffer protein. Using cryo-electron tomography, we showed that CSE is not only essential for Ca2+ homeostasis, but also mediates cell-cell communication via regulating the formation of nanopores -- a necessary precursor of SJs -- as {Delta}cse mutant shows a strong reduction in the number of both nanopores and SJs. This determines for the first time Ca2+-signaling as a novel mechanism controlling cell-cell communication and establishes CSE as a key player regulating cyanobacterial multicellularity. This highlights also Ca2+-signaling as a common conserved principle for regulating cell junctions between organisms that deviated billion years ago.