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

SUMMARY Membrane contact sites (MCS) are fundamental for intracellular communication, but their role in intercellular communication remains unexplored. We show that in plants, plasmodesmata communication bridges function as atypical endoplasmic reticulum (ER)-plasma membrane (PM) tubular MCS, operating at cell-cell interfaces. Similar to other MCS, ER-PM apposition is controlled by a protein-lipid tethering complex, but uniquely, this serves intercellular communication. Combining high-resolution microscopy, molecular dynamics, pharmacological and genetic approaches, we show that cell-cell trafficking is modulated through the combined action of Multiple C2 domains and transmembrane domain proteins (MCTP) 3, 4, and 6 ER-PM tethers, and phosphatidylinositol-4-phosphate (PI4P) lipid. Graded PI4P amounts regulate MCTP docking to the PM, their plasmodesmata localization and cell-cell permeability. SAC7, an ER-localized PI4P-phosphatase, regulates MCTP4 accumulation at plasmodesmata and modulates cell-cell trafficking capacity in a cell-type specific manner. Our findings expand MCS’s functions in information transmission, from intracellular to intercellular cellular activities. In brief Plant intercellular communication is regulated via tubular membrane contact through PI4P binding-ER-PM tether MCTP proteins Highlights Plasmodesmata are unconventional ER/PM tubular contact sites located at cell-cell interface Plasmodesmata operate as control valves, modulating ER-PM contacts to regulate transport MCTP3, MCTP4, MCTP6 and PI4P tethering elements act as valve regulators SAC7 PI4P phosphatase controls plasmodesmata MCS in a cell-type-specific manner