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Ancient Calcium Signaling in Cyanobacterial Cells AI-generated image (ChatGPT 5.6 Sol) Even ancient bacteria possessed intercellular communication structures like humans today | CMFI News The human body is not an organism assembled from newly invented components according to a unique design. It is the latest product of a continuous evolutionary history in which old molecules, old regulatory systems and old cellular capabilities have repeatedly been modified and recruited for new purposes. Even something as fundamental to our existence as communication between neighbouring cells has roots extending far back into the microbial world. Our tissues depend upon cells exchanging ions, metabolites and signals through specialised connections. In animals, structures known as gap junctions form channels between adjacent cells, allowing them to coordinate their activity. They are essential, for example, to the synchronised contraction of heart muscle. Calcium ions also serve as important intracellular signals controlling an enormous range of cellular processes. It might be tempting to regard such coordinated communication as an innovation requiring the complexity of animals or, at the very least, nucleated eukaryotic cells. However, an international research team has shown that a strikingly similar functional principle operates in filament-forming cyanobacteria—organisms belonging to an ancient bacterial lineage. As the researchers report in The EMBO Journal, the cyanobacterium _Nostoc_ sp. PCC 7120 forms long filaments in which neighbouring cells are linked by structures called septal junctions. These pass through arrays of tiny pores in the peptidoglycan partitions between cells, permitting metabolites and signalling molecules to move along the filament. This communication is especially important because some cells can differentiate into specialised nitrogen-fixing cells called heterocysts. These cannot carry out all the metabolic functions of ordinary photosynthetic cells, so the different cell types must exchange nutrients. The filament therefore behaves as an integrated multicellular system in which specialised cells cooperate and depend upon one another. The researchers investigated a small calcium-binding protein called CSE, which is found specifically in multicellular cyanobacteria. Nuclear magnetic resonance spectroscopy showed how CSE folds when it binds calcium, while cryo-electron tomography allowed the team to examine the junctions and nanopores connecting neighbouring cells. When the researchers deleted the gene encoding CSE, the cyanobacterial cells developed fewer nanopores and septal junctions. Communication between cells became slower, some cells ceased communicating altogether, and the normally long filaments fragmented into shorter sections. Restoring the gene restored communication towards its normal rate. The evidence therefore connects calcium regulation through CSE with the formation and operation of the structures that make cyanobacterial multicellularity possible. > How cyanobacterial cells communicate and cooperate. The cyanobacterium _Nostoc_ sp. PCC 7120 does not live merely as a collection of independent cells. Its cells remain attached after division, forming long filaments in which neighbouring cells exchange nutrients and signalling molecules. The filament can therefore operate as an integrated multicellular system. > > When combined nitrogen becomes scarce, some ordinary photosynthetic cells differentiate into specialised cells called **heterocysts**. These use the enzyme nitrogenase to convert atmospheric nitrogen into biologically usable nitrogen compounds. > > Nitrogenase is damaged by oxygen, including the oxygen produced during photosynthesis. Heterocysts therefore suppress oxygen-producing photosynthesis, develop a thicker protective envelope and maintain an internal environment in which nitrogen fixation can proceed. This specialisation creates mutual dependence: > > > * Heterocysts supply neighbouring cells with fixed nitrogen. > * Photosynthetic cells supply heterocysts with carbohydrates and other products of photosynthesis. > * Signals passing along the filament coordinate cell differentiation, metabolism and responses to environmental conditions. > > This division of labour resembles, in a comparatively simple form, the cellular specialisation seen in the tissues of plants and animals. > > Septal junctions > > Adjacent _Nostoc_ cells are separated by membranes and a partition of peptidoglycan—the strong material forming the bacterial cell wall. Arrays of microscopic **nanopores** are drilled through this partition by specialised enzymes. > > Protein structures called **septal junctions** pass through these nanopores and connect the cells on either side. Small molecules can consequently move from one cell to another without first being released into the surrounding environment. This direct exchange helps the cells to coordinate their activities and allows the entire filament to function as a cooperative unit. > > Animal cells also possess direct intercellular connections called **gap junctions**. These are especially important in tissues requiring rapid coordination, including heart muscle, where electrical and chemical signals must spread between neighbouring cells. > Feature | Cyanobacterial septal junctions | Animal gap junctions > ---|---|--- > Organisms | Filamentous multicellular cyanobacteria | Multicellular animals > Location | Between adjacent bacterial cells, passing through the peptidoglycan septum | Between the membranes of adjacent animal cells > Principal function | Exchange of metabolites and signals along the filament | Exchange of ions, metabolites and electrical or chemical signals between cells > Structural proteins | Cyanobacterial septal-junction proteins | Principally connexins in vertebrates > Relationship to calcium | Calcium homeostasis, mediated partly by the CSE protein, regulates nanopore and junction formation | Calcium signalling helps regulate the formation, behaviour and closure of cellular junctions > > Similar principles—not identical structures > > Septal junctions and gap junctions perform comparable functions, but they are constructed from different proteins. The new research does not demonstrate that animal gap junctions descended directly from cyanobacterial septal junctions, nor that human cells inherited the cyanobacterial CSE protein. > > Instead, it suggests that the broader principle of using calcium signals to regulate direct communication between the cells of a multicellular organism is extremely ancient. Whether preserved from a very early biological system or recruited independently in different evolutionary lineages, calcium provided evolution with a useful chemical signalling mechanism long before animals or humans appeared. As the accompanying Heinrich Heine University and University of Tübingen news report explains, calcium also regulates cellular junctions in plants and animals. Cyanobacterial septal junctions are not simply bacterial versions of human gap junctions, nor does this study prove that the two structures share the same direct evolutionary origin. What they share is an underlying functional principle: calcium-based signalling controls communication between the individual cells of a multicellular organism. That principle was therefore not invented for animals, still less for humans. It was already operating in ancient, comparatively simple multicellular organisms and may have been conserved or independently recruited during the subsequent evolution of different forms of multicellularity. Once again, biology reveals not separate creations built from scratch, but continuity, modification and the repeated use of available materials. Evolution did not need to foresee hearts, nervous systems or human bodies. Long before any of those existed, natural selection had already produced cells capable of forming junctions, exchanging materials and coordinating their behaviour. Later evolution inherited an ancient biochemical vocabulary and used it to write increasingly complex variations on the same theme. > Even ancient bacteria possessed intercellular communication structures like humans today > > * * * > > Communication between cells in plants, animals and humans takes place via specialised connecting structures. > > * * * > > Communication between cells in plants, animals and humans takes place via specialised connecting structures. An international team led by biologists from Heinrich Heine University Düsseldorf (HHU) and involving the Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI) at the University of Tübingen has now discovered how the regulation of very similar structures was already present in multicellular bacteria, implying that this must have originated much earlier in the course of evolution. In the scientific journal published by the European Molecular Biology Organization (EMBO), they describe that the exchange of calcium plays a central role in bacteria, just as it does in humans. > > Higher, eukaryotic cells – i.e. cells with a nucleus, such as those found in humans and all higher animals – possess structures that connect neighbouring cells. It is known that, among other things, these structures facilitate fundamental communication processes between cells; without them, tissues such as the human heart could not function. Furthermore, nerve cells transmit the signals that control our bodies via these connecting structures. These structures and the communication between cells are regulated through the exchange of calcium ions (Ca²⁺). > > The research group from the Institute of Phototrophic Microbiology led by Junior Professor Dr Khaled Selim has now discovered that similar communication processes and connecting structures in bacteria are also regulated by calcium signals. Bacteria are however more simple cells that lack a nucleus, so-called prokaryotes. > > It came as a big surprise to us that one of the earliest life forms on Earth – evolutionarily older and simpler cells – had already developed communication structures regulated by calcium signals similar to those found in the cells of higher organisms, such as animals and humans. > > Professor Khaled A. Selim, corresponding author. > Interfaculty Institute of Microbiology and Infection Medicine > Cluster of Excellence “Controlling Microbes to Fight Infections - CMFI” > Tübingen University > Tübingen, Germany. > > > In The EMBO Journal, the research team reports the presence of such communication structures in multicellular cyanobacteria. > > Analogous to the connecting structures in eukaryotes known as gap junctions – traditionally considered a eukaryotic trait – cyanobacteria coordinate their cell-to-cell communication via connecting structures called ‘septum junctions’. The signals regulating this cell-to-cell communication and the formation of septum junctions were previously largely unknown. > > Teresa A. Müller, first author > Interfaculty Institute of Microbiology and Infection Medicine > Cluster of Excellence “Controlling Microbes to Fight Infections - CMFI” > Tübingen University > Tübingen, Germany. > > > The biologists in Düsseldorf discovered a calcium-binding protein (for short: CSE) found exclusively in multicellular cyanobacteria. Using nuclear magnetic resonance (NMR) spectroscopy, they determined the structure of CSE in its calcium-bound state and demonstrated that it functions as a calcium-buffering protein. Furthermore, using cryo-electron microscopy, the researchers observed that the mutant of the bacterial cells lacking CSE exhibited significantly fewer connecting structures. > > Our research offers new insights into evolution. It suggests that the functional principles of higher organisms were already present in simple, multicellular bacteria that form tissue-like structures, meaning that these cellular connections date back a billion years – before the time when the evolutionary lineages of eukaryotes and prokaryotes diverged > > Professor Khaled A. Selim. > > > Publication: > >> Müller, T.A., Stahlecker, F., Roganowicz, K. et al. The calcium-binding protein CSE links Ca2+ signaling with cell-cell communication in cyanobacteria. EMBO J (2026). https://doi.org/10.1038/s44318-026-00893-y > > > Show publication details > Abstract > Multicellular cyanobacteria have evolved sophisticated cell–cell communication machinery to exchange, synchronize, and coordinate the efforts of individual cells. Analogous to gap junctions that have traditionally been regarded as a eukaryotic feature, multicellular cyanobacteria coordinate their cell–cell communication via septal junctions (SJs). However, the signals that regulate cell–cell communication and septal-junction assembly are largely unknown. Lately, calcium signaling has been implicated in regulating cell junctions in eukaryotes. We recently discovered a Ca2+-binding protein, CSE, which is exclusively found in multicellular cyanobacteria. Here, we investigate CSE as a potential link between calcium signaling and cell–cell communication. We solve the NMR structure of CSE in its Ca2+-bound state and revealed that CSE acts as Ca2+-buffer protein. Using cryo-electron tomography, we find that Δcse mutant cells display significantly fewer septal junctions as well as SJ precursors known as nanopores. This indicates that CSE is not only essential for Ca2+ homeostasis, but also mediates cell–cell communication via regulating SJs and nanopores formation, and establishes Ca2+ signaling and CSE as key players regulating cyanobacterial multicellularity. Furthermore, these findings highlight calcium signaling as a conserved principle for regulating cellular junctions in organisms that diverged a billion years ago. > > Synopsis > > > > Multicellular cyanobacteria like _Nostoc_ sp. PCC 7120 build long filaments consisting of connected neighboring cells that exchange molecules through so-called septal junctions. This study shows that loss of the small calcium-binding protein CSE causes disruption of septal junctions and filament fragmentation. > > * The NMR structure of CSE in its Ca2+-bound state reveals Ca2+-induced folding. > * The absence of CSE causes a strong fragmentation phenotype down to small filaments. > * In ∆cse mutant, the septal disks connecting neighboring cells have an increased area with a reduced number of septal junctions and their nanopore precursors. > * Cells lacking CSE show decreased cell-cell communication speed. > > > > > **Movie EV1:** > Cryo-tomogram of a septal region of wildtype Nostoc followed by segmentation, related to (Fig. 6A) and shows normal abundance of septal junctions. Septal junctions are colored in lime green; thylakoid membranes in dark green; peptidoglycan layer and cytoplasmic membranes in gray; granules in yellow. Bar, 100 nm. > > **Movie EV2:** > Cryo-tomogram of a septal region of Δcse mutant followed by segmentation, related to (Fig. 6B) and revealed a strong reduction of septal junctions. Septal junctions are colored in lime green; thylakoid membranes in dark green; peptidoglycan layer and cytoplasmic membranes in gray; granules in yellow. Bar, 100 nm. > > **Movie EV3:** > Cryo-tomogram of a septal region of Δcse mutant followed by segmentation, related to (Fig. EV6), which did not reveal any septal junctions. Thylakoid membranes are colored in dark green; peptidoglycan layer and cytoplasmic membranes in gray; granules in yellow. Bar, 100 nm. > > > > > Müller, T.A., Stahlecker, F., Roganowicz, K. et al. The calcium-binding protein CSE links Ca2+ signaling with cell-cell communication in cyanobacteria. EMBO J (2026). https://doi.org/10.1038/s44318-026-00893-y > > Copyright: © 2026 The authors. > Published by Springer Nature Ltd. Open access. > Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0) The significance of this research lies not merely in the discovery of another bacterial protein, but in what it reveals about the antiquity of coordinated multicellular life. Removing CSE reduced the number of nanopores and septal junctions, slowed communication between neighbouring cells and caused the normally integrated filaments to fragment. Restoring the gene restored normal communication. The relationship between calcium regulation, cellular junctions and filament integrity was therefore demonstrated experimentally, not inferred from superficial resemblance alone. The cyanobacterial and animal structures are not identical, and the study does not show that human gap junctions were inherited unchanged from cyanobacteria. It shows something more fundamental: the use of calcium signalling to regulate direct communication between cooperating cells is an ancient biological principle. Long before animals, nervous systems or beating hearts existed, evolution had produced multicellular organisms whose specialised cells exchanged materials and coordinated their activities through regulated connections. This is precisely the continuity expected from evolution. Natural selection does not discard an effective biochemical mechanism simply because a new lineage or level of complexity arises. Existing molecules and regulatory systems are retained, modified and recruited for new functions. The elaborate communication networks of animal tissues were not conjured into existence fully formed; they were assembled during a long evolutionary history from chemical and cellular capabilities that had already proved useful in much simpler organisms. Creationism contributes nothing to that explanation. Declaring that similar mechanisms were separately installed by an unidentified designer neither explains why they are distributed across such profoundly different organisms nor predicts the experimental results. Evolution, by contrast, gives researchers the framework within which similarities, differences and modifications can be investigated and understood. There was no need for foresight, a plan or a special act of creation. Cells that communicated and cooperated more effectively formed more successful filaments, and natural selection preserved the mechanisms that made that cooperation possible. Human cellular communication is not evidence of our exceptional creation but another reminder that even our most sophisticated biological functions are elaborations of innovations whose origins reach deep into the microbial past. * * * **Advertisement** **Amazon** USA $14.20 UK £11.20 **Amazon** USA $14.15 UK £11.20 **Amazon** USA $12.90 UK £10.00 **Amazon** USA $16.00 UK £12.60 **Amazon** USA $12.50UK £9.30 **Amazon** USA $12.00UK £9.93 **Amazon** USA $12.50UK £10.00 **Amazon** USA $10.50UK £8.30 **Amazon** USA $12.00UK £10.00 **Amazon** USA $15.00UK £12.29 **Amazon** USA $7.50UK £5.75 **Amazon** USA $10.20UK £8.30 **All titles available in paperback, hardcover, ebook for Kindle and audio format.** **Prices correct at time of publication. Click here for current prices.** **Advertisement** Click for My Books ### Thank you for sharing! Tweet Link Blue Sky Flip to Flipboard If you've enjoyed my blog please show your appreciation by giving to a great cause - Oxfam Be Humankind. 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