A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.

The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane proteins. To exit the ER, proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Despite the fundamental role of such cargo receptors in protein tr...

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Autores principales:	Yonatan Herzig, Hayley J Sharpe, Yael Elbaz, Sean Munro, Maya Schuldiner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c8e54a90722e465185194b42b6c2cd2e
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spelling	oai:doaj.org-article:c8e54a90722e465185194b42b6c2cd2e2021-11-18T05:36:38ZA systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.1544-91731545-788510.1371/journal.pbio.1001329https://doaj.org/article/c8e54a90722e465185194b42b6c2cd2e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22629230/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane proteins. To exit the ER, proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Despite the fundamental role of such cargo receptors in protein traffic, only a few have been identified; their cargo spectrum is unknown and the signals they recognize remain poorly understood. We present here an approach we term "PAIRS" (pairing analysis of cargo receptors), which combines systematic genetic manipulations of yeast with automated microscopy screening, to map the spectrum of cargo for a known receptor or to uncover a novel receptor for a particular cargo. Using PAIRS we followed the fate of ∼150 cargos on the background of mutations in nine putative cargo receptors and identified novel cargo for most of these receptors. Deletion of the Erv14 cargo receptor affected the widest range of cargo. Erv14 substrates have a wide array of functions and structures; however, they are all membrane-spanning proteins of the late secretory pathway or plasma membrane. Proteins residing in these organelles have longer transmembrane domains (TMDs). Detailed examination of one cargo supported the hypothesis that Erv14 dependency reflects the length rather than the sequence of the TMD. The PAIRS approach allowed us to uncover new cargo for known cargo receptors and to obtain an unbiased look at specificity in cargo selection. Obtaining the spectrum of cargo for a cargo receptor allows a novel perspective on its mode of action. The rules that appear to guide Erv14 substrate recognition suggest that sorting of membrane proteins at multiple points in the secretory pathway could depend on the physical properties of TMDs. Such a mechanism would allow diverse proteins to utilize a few receptors without the constraints of evolving location-specific sorting motifs.Yonatan HerzigHayley J SharpeYael ElbazSean MunroMaya SchuldinerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 5, p e1001329 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yonatan Herzig Hayley J Sharpe Yael Elbaz Sean Munro Maya Schuldiner A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
description	The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane proteins. To exit the ER, proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Despite the fundamental role of such cargo receptors in protein traffic, only a few have been identified; their cargo spectrum is unknown and the signals they recognize remain poorly understood. We present here an approach we term "PAIRS" (pairing analysis of cargo receptors), which combines systematic genetic manipulations of yeast with automated microscopy screening, to map the spectrum of cargo for a known receptor or to uncover a novel receptor for a particular cargo. Using PAIRS we followed the fate of ∼150 cargos on the background of mutations in nine putative cargo receptors and identified novel cargo for most of these receptors. Deletion of the Erv14 cargo receptor affected the widest range of cargo. Erv14 substrates have a wide array of functions and structures; however, they are all membrane-spanning proteins of the late secretory pathway or plasma membrane. Proteins residing in these organelles have longer transmembrane domains (TMDs). Detailed examination of one cargo supported the hypothesis that Erv14 dependency reflects the length rather than the sequence of the TMD. The PAIRS approach allowed us to uncover new cargo for known cargo receptors and to obtain an unbiased look at specificity in cargo selection. Obtaining the spectrum of cargo for a cargo receptor allows a novel perspective on its mode of action. The rules that appear to guide Erv14 substrate recognition suggest that sorting of membrane proteins at multiple points in the secretory pathway could depend on the physical properties of TMDs. Such a mechanism would allow diverse proteins to utilize a few receptors without the constraints of evolving location-specific sorting motifs.
format	article
author	Yonatan Herzig Hayley J Sharpe Yael Elbaz Sean Munro Maya Schuldiner
author_facet	Yonatan Herzig Hayley J Sharpe Yael Elbaz Sean Munro Maya Schuldiner
author_sort	Yonatan Herzig
title	A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
title_short	A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
title_full	A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
title_fullStr	A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
title_full_unstemmed	A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.
title_sort	systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by erv14.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c8e54a90722e465185194b42b6c2cd2e
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A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.

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