Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells

被引:75
作者
Costello, Joseph L. [1 ]
Castro, Ines G. [1 ,8 ]
Camoes, Fatima [2 ,3 ]
Schrader, Tina A. [1 ]
McNeall, Doug [4 ]
Yang, Jing [5 ]
Giannopoulou, Evdokia-Anastasia [6 ]
Gomes, Silvia [2 ,3 ]
Pogenberg, Vivian [6 ]
Bonekamp, Nina A. [2 ,3 ,9 ]
Ribeiro, Daniela [2 ,3 ]
Wilmanns, Matthias [6 ]
Jedd, Gregory [5 ]
Islinger, Markus [7 ]
Schrader, Michael [1 ,2 ,3 ]
机构
[1] Univ Exeter, Biosci, Exeter EX4 4QD, Devon, England
[2] Univ Aveiro, Ctr Cell Biol, Inst Biomed Dept Biol, P-3810193 Aveiro, Portugal
[3] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal
[4] Met Off, Hadley Ctr, Exeter EX1 3PB, Devon, England
[5] Natl Univ Singapore, Dept Biol Sci, Temasek Life Sci Lab, Singapore, Singapore
[6] DESY, EMBL Hamburg, D-22603 Hamburg, Germany
[7] Heidelberg Univ, Ctr Biomed & Med Technol Mannheim, Inst Neuroanat, D-68167 Mannheim, Germany
[8] Weizmann Inst Sci, Dept Mol Genet, IL-7610001 Rehovot, Israel
[9] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
Tail-anchored protein; Peroxisomes; Mitochondria; ACBD5; PEROXISOMAL MEMBRANE-PROTEINS; MITOCHONDRIAL OUTER-MEMBRANE; ENDOPLASMIC-RETICULUM; INTEGRATION; COMPLEX; DEGRADATION; SPECIFICITY; INSERTION; CONTAINS; MUTATION;
D O I
10.1242/jcs.200204
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the C-terminus that anchors them to the membranes of organelles where they mediate critical cellular processes. Accordingly, mutations in genes encoding TA proteins have been identified in a number of severe inherited disorders. Despite the importance of correctly targeting a TA protein to its appropriate membrane, the mechanisms and signals involved are not fully understood. In this study, we identify additional peroxisomal TA proteins, discover more proteins that are present on multiple organelles, and reveal that a combination of TMD hydrophobicity and tail charge determines targeting to distinct organelle locations in mammals. Specifically, an increase in tail charge can override a hydrophobic TMD signal and re-direct a protein from the ER to peroxisomes or mitochondria and vice versa. We show that subtle changes in those parameters can shift TA proteins between organelles, explaining why peroxisomes and mitochondria have many of the same TA proteins. This enabled us to associate characteristic physicochemical parameters in TA proteins with particular organelle groups. Using this classification allowed successful prediction of the location of uncharacterized TA proteins for the first time.
引用
收藏
页码:1675 / 1687
页数:13
相关论文
共 74 条
[61]   PeroxisomeDB:: a database for the peroxisomal proteome, functional genomics and disease [J].
Schluter, Agatha ;
Fourcade, Stephane ;
Domenech-Estevez, Enric ;
Gabaldon, Toni ;
Huerta-Cepas, Jaime ;
Berthommier, Guillaume ;
Ripp, Raymond ;
Wanders, Ronald J. A. ;
Poch, Olivier ;
Pujol, Aurora .
NUCLEIC ACIDS RESEARCH, 2007, 35 :D815-D822
[62]   Peroxisome-mitochondria interplay and disease [J].
Schrader, Michael ;
Costello, Joseph ;
Godinho, Luis F. ;
Islinger, Markus .
JOURNAL OF INHERITED METABOLIC DISEASE, 2015, 38 (04) :681-702
[63]   The GET complex mediates insertion of tail-anchored proteins into the ER membrane [J].
Schuldiner, Maya ;
Metz, Jutta ;
Schmid, Volker ;
Denic, Vladimir ;
Rakwalska, Magdalena ;
Schmitt, Hans Dieter ;
Schwappach, Blanche ;
Weissman, Jonathan S. .
CELL, 2008, 134 (04) :634-645
[64]   Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteins [J].
Setoguchi, Kiyoko ;
Otera, Hidenori ;
Mihara, Katsuyoshi .
EMBO JOURNAL, 2006, 25 (24) :5635-5647
[65]   Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes [J].
Shamseldin, Hanan E. ;
Alshammari, Muneera ;
Al-Sheddi, Tarfa ;
Salih, Mustafa A. ;
Alkhalidi, Hisham ;
Kentab, Amal ;
Repetto, Gabriela M. ;
Hashem, Mais ;
Alkuraya, Fowzan S. .
JOURNAL OF MEDICAL GENETICS, 2012, 49 (04) :234-241
[66]   Development of a prediction system for tail-anchored proteins [J].
Shigemitsu, Shunsuke ;
Cao, Wei ;
Terada, Tohru ;
Shimizu, Kentaro .
BMC BIOINFORMATICS, 2016, 17
[67]  
Stoffel W., 1993, BIOL CHEM HOPPESEYLE, V374, P166, DOI [DOI 10.1016/J.JTBI.2009.11.002, DOI 10.1515/BCHM3.1993.374.1-6.143]
[68]   Protein production by auto-induction in high-density shaking cultures [J].
Studier, FW .
PROTEIN EXPRESSION AND PURIFICATION, 2005, 41 (01) :207-234
[69]   WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane [J].
Vilardi, Fabio ;
Lorenz, Holger ;
Dobberstein, Bernhard .
JOURNAL OF CELL SCIENCE, 2011, 124 (08) :1301-1307
[70]  
Vogl C., 2016, EMBO J, V31, P17