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bioRxiv · 10.1101/122028

A Di-Acidic Motif Targets Cytoplasmic Proteins For Unconventional Protein Secretion

Cruz-Garcia, D.·Brouwers, N.·Duran, J. M.·Curwin, A. J.·Malhotra, V.
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Abstract

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.

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Cruz-Garcia, D., Brouwers, N., Duran, J. M., Curwin, A. J., Malhotra, V.. 2017-03-29. A Di-Acidic Motif Targets Cytoplasmic Proteins For Unconventional Protein Secretion. https://doi.org/10.1101/122028

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