Eisosomes as platforms for lipid signalling Free

The plasma membranes of all eukaryotic cells consist of stable compartments or microdomains that allow for a wide range of cellular functions. In yeast cells, a prominent cortical microdomain appears as a series of linear invaginations, called eisosomes, that each contain several thousand copies of the BAR protein Pil1. However, despite extensive studies in different yeast species, the exact role of eisosomes remains enigmatic. On page 1318, James Moseley and colleageus set out to elucidate their function in the fission yeast Schizosaccharomyces pombe – an ideal model system as its eisosomes are simple and, in addition to Pil1, only contain the transmembrane protein Fhn1 and the peripheral membrane protein Sle1. By using a combination of genetic and biochemical approaches, the authors find that Pil1 and Sle1 function with the synaptojanin-like lipid phosphatase Syj1, which regulates the hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂]. This functional link between eisosomes and PtdIns(4,5)P₂ led them to examine the effect of altered regulation of this lipid and, indeed, confirmed that correct eisosome assembly requires the dynamic generation and hydrolysis of PtdIns(4,5)P₂. Moreover, the authors show that signal transduction mediated by target of rapamycin complex 2 (TORC2) is controlled by the eisosome-synaptojanin pathway, indicating that regulation of PtdIns(4,5)P₂ by eisosomes might act as an upstream signal for this pathway. Finally, the authors note that the membrane geometry of eisosomes is similar to caveolae in animal cells, which raises the interesting possibility that they have evolved to fulfil similar function; but this will require further investigation.