title: RhoA regulates peroxisome association to microtubules and the actin cytoskeleton.
abstract: The current view of peroxisome inheritance provides for the formation of new peroxisomes by both budding from the endoplasmic reticulum and autonomous division. Here we investigate peroxisome-cytoskeleton interactions and show by proteomics, biochemical and immunofluorescence analyses that actin, non-muscle myosin IIA (NMM IIA), RhoA, Rho kinase II (ROCKII) and Rab8 associate with peroxisomes. Our data provide evidence that (i) RhoA in its inactive state, maintained for example by C. botulinum toxin exoenzyme C3, dissociates from peroxisomes enabling microtubule-based peroxisomal movements and (ii) dominant-active RhoA targets to peroxisomes, uncouples the organelles from microtubules and favors Rho kinase recruitment to peroxisomes. We suggest that ROCKII activates NMM IIA mediating local peroxisomal constrictions. Although our understanding of peroxisome-cytoskeleton interactions is still incomplete, a picture is emerging demonstrating alternate RhoA-dependent association of peroxisomes to the microtubular and actin cytoskeleton. Whereas association of peroxisomes to microtubules clearly serves bidirectional, long-range saltatory movements, peroxisome-acto-myosin interactions may support biogenetic functions balancing peroxisome size, shape, number, and clustering.
authors.affiliation: Heidelberg Center of Biochemistry, University of Heidelberg, Heidelberg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Schollenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Gronemeyer
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Huber
authors.forename: Dorothee
authors.initials: D
authors.lastname: Lay
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiese
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.forename: Johan
authors.initials: J
authors.lastname: Peränen
authors.forename: Karin
authors.initials: K
authors.lastname: Gorgas
authors.forename: Wilhelm W
authors.initials: WW
authors.lastname: Just
mesh_terms: D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003599:Cytoskeleton / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D000199:Actins; C521976:Rab8 protein, mouse; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D054460:rho-Associated Kinases; D024507:Nonmuscle Myosin Type IIA; D020691:rab GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein