Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells
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Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells. / Costello, Joseph L; Castro, Inês G; Camões, Fátima; Schrader, Tina A; McNeall, Doug; Yang, Jing; Giannopoulou, Evdokia-Anastasia; Gomes, Sílvia; Pogenberg, Vivian; Bonekamp, Nina A; Ribeiro, Daniela; Wilmanns, Matthias; Jedd, Gregory; Islinger, Markus; Schrader, Michael.
In: J CELL SCI, Vol. 130, No. 9, 01.05.2017, p. 1675-1687.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells
AU - Costello, Joseph L
AU - Castro, Inês G
AU - Camões, Fátima
AU - Schrader, Tina A
AU - McNeall, Doug
AU - Yang, Jing
AU - Giannopoulou, Evdokia-Anastasia
AU - Gomes, Sílvia
AU - Pogenberg, Vivian
AU - Bonekamp, Nina A
AU - Ribeiro, Daniela
AU - Wilmanns, Matthias
AU - Jedd, Gregory
AU - Islinger, Markus
AU - Schrader, Michael
N1 - © 2017. Published by The Company of Biologists Ltd.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Compartmentation
KW - Endoplasmic Reticulum/metabolism
KW - Hep G2 Cells
KW - Humans
KW - Hydrophobic and Hydrophilic Interactions
KW - Intracellular Membranes/metabolism
KW - Mammals/metabolism
KW - Membrane Proteins/chemistry
KW - Mitochondria/metabolism
KW - Models, Biological
KW - Peroxisomes/metabolism
KW - Protein Transport
KW - Saccharomyces cerevisiae/metabolism
KW - Subcellular Fractions/metabolism
U2 - 10.1242/jcs.200204
DO - 10.1242/jcs.200204
M3 - SCORING: Journal article
C2 - 28325759
VL - 130
SP - 1675
EP - 1687
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 9
ER -