Making connections: control of PI kinase signaling at ER-PM junctions

Information transfer between intracellular organelles must take place to regulate the size, shape, composition, and function of individual organelles, as well as for normal cell growth and development. The endoplasmic reticulum (ER) forms an expansive membrane network that contacts and participates in crosstalk with several other organelles in the cell, most notably the plasma membrane (PM). ER-PM junctions have well-established functions in the movement of signaling molecules, such as lipids and ions, between the ER and PM. However, little is known about the architecture and structural components of ER-PM junctions. Using a quantitative proteomics approach, we have identified three families of ER-PM tether proteins in yeast: the VAP proteins Scs2/22, Ist2 (related to the TMEM16 channel family), and the tricalbin proteins Tcb1/2/3 (orthologs of the extended synaptotagmin-like proteins E-Syt1/2/3). Loss of the ER tether proteins results in separation of the peripheral ER network from the PM and the accumul...