Mechanisms of Selective Protein Secretion

Abstract

Secretory and membrane proteins account for a third of the eukaryotic proteome, and play important roles in tissue organization, nutrient uptake and cell-cell communication. To function in these roles, each protein must be correctly folded, post-translationally modified and delivered to the appropriate compartment. The speaker’s long-term aim is to define the mechanisms by which protein synthesis and vesicle formation machineries are tuned to match the specific physiological needs of a cell. In this talk, she will describe the recent work on the mechanisms by which an export receptor, SURF4, bridges interactions between soluble secretory proteins within the lumen of the endoplasmic reticulum (ER) and the vesicle budding machinery that delivers cargo to the Golgi. SURF4 recognizes a hydrophobic sorting motif on its client cargo via a membrane-embedded pocket, and interacts with the SEC24 cargo adaptor component of the COPII budding machinery by multiple cytoplasmic signals. The research team used a small molecule that occludes the site of interaction between SEC24 and SURF4 to show that this drug reduces secretion of a subset of the secretome, raising the exciting possibility that protein secretion can be selectively drugged for therapeutic benefit.

About the Speaker

Prof. Elizabeth Ann MILLER is one of the leading experts in the field of membrane trafficking, particularly in the area of ER export and the quality control checkpoint during membrane protein biogenesis. She gained her Bachelor's degree in Botany and Zoology at the University of Melbourne, Australia and PhD degree in Cell Biology at La Trobe University, Melbourne, Australia. She worked with the Nobel laureate Prof. Randy SCHEKMAN at the University of California at Berkeley as a postdoc working on molecular mechanisms of cargo sorting at the endoplasmic reticulum. Prof. Miller joined the faculty of Department of Biological Sciences, Columbia University as an Assistant Professor in 2005 and Associate Professor with tenure in 2013. In 2015, she became the Programme Leader of the MRC Laboratory of Molecular Biology. She is currently Professor of Molecular Cell and Developmental Biology at University of Dundee.

Prof. Miller's research focuses on understanding the basic mechanisms of secretory protein biogenesis, focusing on protein quality control within the endoplasmic reticulum. Her lab uses the budding yeast as a model system, and has discovered new pathways and dissected mechanisms that may be directly relevant to a number of human diseases, most notably cystic fibrosis and similar diseases of protein misfolding.

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