Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria.
Mouse kif5B gene was disrupted by homologous recombination. kif5B-/- mice were embryonic lethal with a severe growth retardation at 9.5-11.5 days postcoitum. To analyze the significance of this conventional kinesin heavy chain in organelle transport, we studied the distribution of major organelles in the extraembryonic cells. The null mutant cells impaired lysosomal dispersion, while brefeldin A could normally induce the breakdown of their Golgi apparatus. More prominently, their mitochondria abnormally clustered in the perinuclear region. This mitochondrial phenotype was reversed by an exogenous expression of KIF5B, and a subcellular fractionation revealed that KIF5B is associated with mitochondria. These data collectively indicate that kinesin is essential for mitochondrial and lysosomal dispersion rather than for the Golgi-to-ER traffic in these cells.
Tanaka
Y
Y
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo, Japan.
Kanai
Y
Y
Okada
Y
Y
Nonaka
S
S
Takeda
S
S
Harada
A
A
Hirokawa
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020126:Brefeldin A; D002458:Cell Fractionation; D002467:Cell Nucleus; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal / Q000235:genetics; D006056:Golgi Apparatus / Q000187:drug effects; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology; D018942:Macrolides; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D015017:Yolk Sac / Q000166:cytology
D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; D018942:Macrolides; D012333:RNA, Messenger; D020126:Brefeldin A; D016547:Kinesins; D015739:Nocodazole