title: Identification of the kinesin KifC3 as a new player for positioning of peroxisomes and other organelles in mammalian cells.
abstract: The attachment of organelles to the cytoskeleton and directed organelle transport is essential for cellular morphology and function. In contrast to other cell organelles like the endoplasmic reticulum or the Golgi apparatus, peroxisomes are evenly distributed in the cytoplasm, which is achieved by binding of peroxisomes to microtubules and their bidirectional transport by the microtubule motor proteins kinesin-1 (Kif5) and cytoplasmic dynein. KifC3, belonging to the group of C-terminal kinesins, has been identified to interact with the human peroxin PEX1 in a yeast two-hybrid screen. We investigated the potential involvement of KifC3 in peroxisomal transport. Interaction of KifC3 and the AAA-protein (ATPase associated with various cellular activities) PEX1 was confirmed by in vivo colocalization and by coimmunoprecipitation from cell lysates. Furthermore, knockdown of KifC3 using RNAi resulted in an increase of cells with perinuclear-clustered peroxisomes, indicating enhanced minus-end directed motility of peroxisomes. The occurrence of this peroxisomal phenotype was cell cycle phase independent, while microtubules were essential for phenotype formation. We conclude that KifC3 may play a regulatory role in minus-end directed peroxisomal transport for example by blocking the motor function of dynein at peroxisomes. Knockdown of KifC3 would then lead to increased minus-end directed peroxisomal transport and cause the observed peroxisomal clustering at the microtubule-organizing center.
authors: Interfaculty Institute of Biochemistry, Cell Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany.
authors: Denise
authors: D
authors: Dietrich
authors: Interfaculty Institute of Biochemistry, Cell Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany.
authors: Florian
authors: F
authors: Seiler
authors: Interfaculty Institute of Biochemistry, Molecular Medicine, University of Tuebingen, D-72076 Tuebingen, Germany.
authors: Frank
authors: F
authors: Essmann
authors: Interfaculty Institute of Biochemistry, Cell Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany. Electronic address: gabriele.dodt@uni-tuebingen.de.
authors: Gabriele
authors: G
authors: Dodt
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D016000:Cluster Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015388:Organelles / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding
chemical_list: C586505:Kifc3 protein, human; C419428:Kifc3 protein, mouse; D008565:Membrane Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C111808:PEX1 protein, human; D016547:Kinesins
keywords: 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid; AAA-protein; ATPase associated with diverse cellular activities; CLIP; CoIp; Coimmunoprecipitation; Cytoskeleton; EEA; GAPDH; HEPES; Kif; Kinesins; MAPK; MDCK-II cells; Madin Darby canine kidney II cells; PEX; PMP; PTS-1; Peroxins; Peroxisomes; TGN; cytoplasmic linker protein; early endosomal antigen; glyceraldehyde 3-phosphate dehydrogenase; kinesin superfamily protein; mitogen-activated protein kinase; peroxin; peroxisomal membrane protein; peroxisomal targeting sequence-1; trans-Golgi network