Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of cultured hippocampal neurons.
The mitochondria in the axons and dendrites of neurons are highly motile, but the mechanism of these movements is not well understood. It has been thought that the transport of membrane-bounded organelles in axons, and perhaps also in dendrites, depends on molecular motors of the kinesin and dynein families. However, recent evidence has suggested that some organelle transport, including that of mitochondria, may proceed along actin filaments as well. The present study sought to determine the extent to which mitochondrial movements in neurons depend on microtubule-based and actin-based transport systems. The mitochondria in cultured hippocampal neurons were labeled with a fluorescent dye and the cells were treated with either nocodazole, a drug that disrupts the microtubule network or cytochalasin D or latrunculin B, drugs which disrupt the actin network. The movement of the mitochondria in the axons and dendrites of neurons after each of these drug treatments was then examined with time-lapse microscopy. Treatment with nocodazole, which depolymerizes microtubules, stopped most mitochondrial movements in both axons and dendrites. Treatment with cytochalasin D, which aggregates actin filaments, also inhibited most movements of mitochondria, but latrunculin B, which depolymerizes actin filaments, had virtually no effect. Together, these data suggest that most of the mitochondrial movements in both axons and dendrites are microtubule-based, but in each domain there may also be some movement along actin filaments.
Ligon
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Department of Neuroscience and the Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia 22908, USA.
Steward
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D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019384:Nucleic Acid Synthesis Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; C037068:latrunculin B; D015739:Nocodazole