Bat3 promotes the membrane integration of tail-anchored proteins
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Bat3 promotes the membrane integration of tail-anchored proteins. / Leznicki, Pawel; Clancy, Anne; Schwappach, Blanche; High, Stephen.
in: J CELL SCI, Jahrgang 123, Nr. Pt 13, 01.07.2010, S. 2170-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Bat3 promotes the membrane integration of tail-anchored proteins
AU - Leznicki, Pawel
AU - Clancy, Anne
AU - Schwappach, Blanche
AU - High, Stephen
PY - 2010/7/1
Y1 - 2010/7/1
N2 - The membrane integration of tail-anchored proteins at the endoplasmic reticulum (ER) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. For example, mammalian TRC40 has a well-defined role during delivery of tail-anchored proteins to the ER. Although its Saccharomyces cerevisiae equivalent, Get3, is known to function in concert with at least four other components, Get1, Get2, Get4 and Get5 (Mdy2), the role of additional mammalian proteins during tail-anchored protein biogenesis is unclear. To this end, we analysed the cytosolic binding partners of Sec61beta, a well-defined substrate of TRC40, and identified Bat3 as a previously unknown interacting partner. Depletion of Bat3 inhibits the membrane integration of Sec61beta, but not of a second, TRC40-independent, tail-anchored protein, cytochrome b5. Thus, Bat3 influences the in vitro membrane integration of tail-anchored proteins using the TRC40 pathway. When expressed in Saccharomyces cerevisiae lacking a functional GET pathway for tail-anchored protein biogenesis, Bat3 associates with the resulting cytosolic pool of non-targeted chains and diverts it to the nucleus. This Bat3-mediated mislocalisation is not dependent upon Sgt2, a recently identified component of the yeast GET pathway, and we propose that Bat3 either modulates the TRC40 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins.
AB - The membrane integration of tail-anchored proteins at the endoplasmic reticulum (ER) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. For example, mammalian TRC40 has a well-defined role during delivery of tail-anchored proteins to the ER. Although its Saccharomyces cerevisiae equivalent, Get3, is known to function in concert with at least four other components, Get1, Get2, Get4 and Get5 (Mdy2), the role of additional mammalian proteins during tail-anchored protein biogenesis is unclear. To this end, we analysed the cytosolic binding partners of Sec61beta, a well-defined substrate of TRC40, and identified Bat3 as a previously unknown interacting partner. Depletion of Bat3 inhibits the membrane integration of Sec61beta, but not of a second, TRC40-independent, tail-anchored protein, cytochrome b5. Thus, Bat3 influences the in vitro membrane integration of tail-anchored proteins using the TRC40 pathway. When expressed in Saccharomyces cerevisiae lacking a functional GET pathway for tail-anchored protein biogenesis, Bat3 associates with the resulting cytosolic pool of non-targeted chains and diverts it to the nucleus. This Bat3-mediated mislocalisation is not dependent upon Sgt2, a recently identified component of the yeast GET pathway, and we propose that Bat3 either modulates the TRC40 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins.
KW - Adenosine Triphosphate/metabolism
KW - Animals
KW - Carrier Proteins/genetics
KW - Cell Membrane/metabolism
KW - Cytosol/metabolism
KW - Humans
KW - Membrane Proteins/genetics
KW - Membrane Transport Proteins/genetics
KW - Molecular Chaperones/genetics
KW - Qa-SNARE Proteins/genetics
KW - Recombinant Fusion Proteins/genetics
KW - SEC Translocation Channels
KW - Saccharomyces cerevisiae/cytology
KW - Saccharomyces cerevisiae Proteins/genetics
KW - Signal Transduction/physiology
U2 - 10.1242/jcs.066738
DO - 10.1242/jcs.066738
M3 - SCORING: Journal article
C2 - 20516149
VL - 123
SP - 2170
EP - 2178
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - Pt 13
ER -