Peroxisome formation requires the endoplasmic reticulum channel protein Sec61.
In peroxisome formation, models of near-autonomous peroxisome biogenesis with membrane protein integration directly from the cytosol into the peroxisomal membrane are in direct conflict with models whereby peroxisomes bud from the endoplasmic reticulum and receive their membrane proteins through a branch of the secretory pathway. We therefore reinvestigated the role of the Sec61 complex, the protein-conducting channel of the endoplasmic reticulum (ER) in peroxisome formation. We found that depletion or partial inactivation of Sec61 in yeast disables peroxisome formation. The ER entry of the early peroxisomal membrane protein Pex3 engineered with a glycosylation tag is reduced in sec61 mutant cells. Moreover, we were able to reconstitute Pex3 import into ER membranes in vitro, and we identified a variant of a signal anchor sequence for ER translocation at the Pex3 N-terminus. Our findings are consistent with a Sec61 requirement for peroxisome formation and a fundamental role of the ER in peroxisome biogenesis.
Department of Pediatrics and Pediatric Neurology, University Medical Center, Georg August University of Göttingen, 37075, Göttingen, Germany. sven.thoms@med.uni-goettingen.de
Sven
S
Thoms
Imke
I
Harms
Kai-Uwe
KU
Kalies
Jutta
J
Gärtner
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D000074401:Peroxins; D020675:Peroxisomes / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C070895:PEX3 protein, S cerevisiae; D000074401:Peroxins; D000069816:SEC Translocation Channels; D029701:Saccharomyces cerevisiae Proteins