Bat3 promotes the membrane integration of tail-anchored proteins.
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.
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Pawel
P
Leznicki
Anne
A
Clancy
Blanche
B
Schwappach
Stephen
S
High
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
C092009:BAG6 protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; C499388:SEC61B protein, human; D029701:Saccharomyces cerevisiae Proteins; C077554:Sed5 protein, S cerevisiae; C520576:Sgt2 protein, S cerevisiae; D000255:Adenosine Triphosphate