TY - JOUR T1 - A di-acidic motif targets cytoplasmic proteins for unconventional protein secretion JF - bioRxiv DO - 10.1101/122028 SP - 122028 AU - David Cruz-Garcia AU - Nathalie Brouwers AU - Juan M. Duran AU - Amy J. Curwin AU - Vivek Malhotra Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/29/122028.abstract N2 - We previously reported that Acb1, a cytoplasmic protein in Saccharomyces cerevisiae that cannot enter the endoplasmic reticulum (ER), was secreted upon nutrient starvation by a Vps4 independent, but ESCRT-I, -II and -III and Grh1 dependent pathway (Curwin et al., 2016). Here, we report that the same conditions result in secretion of another signal sequence lacking protein, superoxide dismutase 1 (SOD1). Similar to Acb1, SOD1 export requires Grh1 and a subset of ESCRT components. Importantly, our analysis reveals the existence of a conserved di-acidic motif (Asp-Glu) in SOD1 and Acb1 that is required for their respective export. This sequence is different from the di-acidic motif (Asp-X-Glu) necessary for export of transmembrane proteins from the ER. We propose that the Asp-Glu sequence acts as a targeting motif for the entry of SOD1 and Acb1, and likely many other proteins, upon nutrient starvation into a common albeit ER-Golgi independent pathway of secretion. ER -