A Systematic Approach to Pair Secretory Cargo Receptors with Their Cargo Suggests a Mechanism for Cargo Selection by Erv14

Yonatan Herzig,Yael Elbaz,Maya Schuldiner,Hayley J Sharpe,Sean Munro,Sandra L Schmid

doi:10.1371/journal.pbio.1001329

Yonatan Herzig, Yael Elbaz + Show 4 more

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https://doi.org/10.1371/journal.pbio.1001329

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Abstract

Author SummaryAll cells sense their environment, respond to it, and communicate with neighboring cells. To perform these functions, cells use an impressive array of proteins that they display on their surface membranes and secrete into their external environment. Newly synthesized proteins destined for the surface of nucleated cells, or to be secreted into the environment must enter the secretory pathway through the endoplasmic reticulum. Those that reside there remain behind, but most leave for their next destination as cargo proteins in lipid vesicles. To be packaged into vesicles, many of them require a “cargo receptor,” which recognizes and tethers specific cargo proteins in the vesicles. Our study takes a systematic approach to identify the range of cargo proteins that bind to each of the known receptors in yeast. By using this approach, we both discover new cargo for known cargo receptors and delineate the rule that governs cargo selection for one cargo receptor, Erv14. Thus, our study demonstrates a novel approach to identify the cargo for any receptor or to discover new cargo receptors.

Highlights

The endoplasmic reticulum (ER) is the entry site into the secretory pathway, responsible for the folding, maturation, and trafficking of all secreted, membrane-bound, and secretory pathway resident proteins
Synthesized proteins destined for the surface of nucleated cells, or to be secreted into the environment must enter the secretory pathway through the endoplasmic reticulum
Our study demonstrates a novel approach to identify the cargo for any receptor or to discover new cargo receptors

Summary

Introduction

The endoplasmic reticulum (ER) is the entry site into the secretory pathway, responsible for the folding, maturation, and trafficking of all secreted, membrane-bound, and secretory pathway resident proteins. Because of the complexity of these approaches, only a few additional cargo receptors have since been identified (Table S1) Despite their important function in ER exit and their potential for regulating the flow of traffic in the entire secretory pathway, there is still little information about the entire spectrum of cargos for a given cargo receptor or what defines its cargo specificity. The lack of systematic data has hindered the identification of the determinants shared by specific sets of cargo that allow their recognition by a particular cargo receptor. Identification of such determinants might shed light on the purpose and mechanism of action by which a given cargo receptor operates

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