Inter-organelle communication can be mediated at membrane contact sites where two organelles are in close contact to each other within 10-30 nm, permitting direct molecular interactions. Contact sites formed between the endoplasmic reticulum (ER) and the plasma membrane (PM), known as the triad or dyad junctions, have been shown to be important for excitation-contraction (E-C) coupling for muscle functions several decades ago. The identification of STIM1 that mediates store-operated calcium entry ( SOCE) at ER-PM junctions revealed the general importance of ER-PM junctions in calcium signaling in all mammalian cells. We aim to understand how ER-PM junctions are formed and regulated by developing genetically-encoded markers and imaging methods to track these junctions in live cells, and by performing proteomic analysis to identify proteins selectively localize at ER-PM junctions. In addition, we are investigating signaling events occurring at ER-PM junctions and their functional significance to cell physiology.
Our research has contributed to
- Development of MAPPER that selectively labels ER-PM junctions based on the targeting mechanism of STIM1
- Identification of E-Syt1 and Nir2 that dynamically localize to ER-PM junctions and mediate PI(4,5)P2 replenishment during calcium signaling