The endomembrane system is critical for all cellular organisms from fungi to plants to humans as a means to proportion proteins, lipids and metabolites within cells, for communication between cells and for pathogen defense. The system is composed of a network of membrane organelles (ER, Golgi, trans-Golgi network, endosomes, multi-vesicular bodies) through which proteins are transported to vacuoles/lysosomes, the secretory pathway or the recycling pathway. Our lab studies these basic processes in the plant Arabidopsis by taking advantage of excellent genomics, genetics and cell biology. The endomembrane network is essential in plants for coordinated growth and development. Although trafficking-related genes are conserved across kingdoms, plants have evolved unique adaptations because they cannot flee from environment or predators.
We have developed plant based large-scale screening approaches to identify novel regulators of plant growth and development. We have identified novel small synthetic molecules that inhibit pollen germination or tube growth in vitro using automated microscopy. This tip growth requires exocytosis, endocytosis and other conserved endomembrane trafficking processes that are essential for plant agricultural traits such as secretion, storage protein accumulation, root and leaf development, and water absorption among others. In plants, key plasma membrane proteins such as PIN auxin hormone transporters and the BRI1 brassinosteroid receptor translocate dynamically between endosomes, plasma membrane and vacuole, controlling their abundance at specific sites of action such as the plasma membrane. Using essentially a drug screening approach we identified small molecules that affect trafficking of PIN auxin transporters and other plasma membrane proteins that determine plant architecture. We have shown that one of these compounds (ES2) targets the EXO70A1 component of the exocyst complex which targets secretory vesicles to the plasma membrane and is essential for normal development. Recently, we have focused on compounds that affect vesicle trafficking to the vacuole. A new compound (ES17) interferes with late vesicle fusion at the vacuole by targeting a specific vesicle-tethering complex. ES17 also appears to affect autophagy providing a connection between these processes. More broadly, these trafficking processes have been implicated in neurodegenerative diseases such as Parkinson, ALS and Alzheimer’s and thus discovering the cognate targets of endomembrane-active chemicals may have value beyond plant biology.