The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission.
The initial phase of peroxisomal fission requires the peroxisomal membrane protein Peroxin 11 (Pex11p), which remodels the membrane, resulting in organelle elongation. Here, we identify an additional function for Pex11p, demonstrating that Pex11p also plays a crucial role in the final step of peroxisomal fission: dynamin-like protein (DLP)-mediated membrane scission. First, we demonstrate that yeast Pex11p is necessary for the function of the GTPase Dynamin-related 1 (Dnm1p) in vivo. In addition, our data indicate that Pex11p physically interacts with Dnm1p and that inhibiting this interaction compromises peroxisomal fission. Finally, we demonstrate that Pex11p functions as a GTPase activating protein (GAP) for Dnm1p in vitro. Similar observations were made for mammalian Pex11β and the corresponding DLP Drp1, indicating that DLP activation by Pex11p is conserved. Our work identifies a previously unknown requirement for a GAP in DLP function.
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and.
Chris
http://orcid.org/0000-0003-1757-6156
C
Williams
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, 9747 AG Groningen, The Netherlands;
Lukasz
L
Opalinski
Institut für Medizinische Immunologie, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany;
Christiane
C
Landgraf
College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter EX4 4QD, United Kingdom; and.
Joseph
J
Costello
College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter EX4 4QD, United Kingdom; and.
Michael
M
Schrader
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, 9747 AG Groningen, The Netherlands;
Arjen M
AM
Krikken
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and.
Kèvin
K
Knoops
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, 9747 AG Groningen, The Netherlands;
Anita M
AM
Kram
Institut für Medizinische Immunologie, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany; Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
Rudolf
R
Volkmer
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, 9747 AG Groningen, The Netherlands; i.j.van.der.klei@rug.nl.
Ida J
IJ
van der Klei
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D007425:Intracellular Membranes / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D000074401:Peroxins; D020675:Peroxisomes / Q000502:physiology*; D010843:Pichia; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092128:PEX11 protein, S cerevisiae; D000074401:Peroxins; D029701:Saccharomyces cerevisiae Proteins; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae
DLP; GAP; GTPase activating protein; dynamin-like protein; organelle fission