Should I stay or should I go – does protein localisation to plasmodesmata depend on targeting signals?

Plasmodesmata (PDs), the cell junctions of plants, are specialized plasma membrane (PM)–endoplasmic reticulum (ER) contact sites structured as nanochannels providing intercellular cytoplasmic and membrane continuity. Given their importance, the identification of structural and functional PD proteins has long been a research aim. Discovering conserved PD localization signals would allow prediction of PD proteins and artificial PD targeting. Proteomic studies have now identified many bona fide PD proteins, and various sequence motifs responsible for PD localization have been characterized. However, no conserved targeting signals have emerged. Here, we ask if a focus on protein PD targeting might be a misleading concept.