Plasmodesmata act as unconventional membrane contact sites regulating inter-cellular molecular exchange in plants

Membrane contact sites (MCSs) are fundamental actors of intracellular communication, but their role in intercellular communication remains unexplored. Here we show that in plants, plasmodesmata cytoplasmic bridges function as atypical endoplasmic reticulum (ER)-plasma membrane (PM) tubular MCSs, operating at cell-cell interfaces. Similar to other MCSs, ER-PM apposition within plasmodesmata is controlled by a protein-lipid tethering complex. Unlike other MCS however, regulation of membrane contacts primarily serves intercellular communication. Plasmodesmata MCSs act as flow-control valves, effectively regulating molecular transport between cells, by modulating the ER-PM passage size. This occurs through the collaborative action of the ER-anchored Multiple C2 domains and transmembrane domain proteins (MCTP) 3, 4, and 6 tether-complex, and PM-localized PI4P lipid as a binding partner. The MCS flow-control mechanism overrides the well-established plasmodesmata regulator callose, rendering plasmodesmata unable to close in MCTPs absence. Our findings highlight MCS's diversified functions in transmitting information, spanning from intracellular to intercellular cellular activities. ### Competing Interest Statement The authors have declared no competing interest.