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  • 1
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    Optogenetic control of organelle transport and positioning (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-01-07
    Description: Proper positioning of organelles by cytoskeleton-based motor proteins underlies cellular events such as signalling, polarization and growth. For many organelles, however, the precise connection between position and function has remained unclear, because strategies to control intracellular organelle positioning with spatiotemporal precision are lacking. Here we establish optical control of intracellular transport by using light-sensitive heterodimerization to recruit specific cytoskeletal motor proteins (kinesin, dynein or myosin) to selected cargoes. We demonstrate that the motility of peroxisomes, recycling endosomes and mitochondria can be locally and repeatedly induced or stopped, allowing rapid organelle repositioning. We applied this approach in primary rat hippocampal neurons to test how local positioning of recycling endosomes contributes to axon outgrowth and found that dynein-driven removal of endosomes from axonal growth cones reversibly suppressed axon growth, whereas kinesin-driven endosome enrichment enhanced growth. Our strategy for optogenetic control of organelle positioning will be widely applicable to explore site-specific organelle functions in different model systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Bergeijk, Petra -- Adrian, Max -- Hoogenraad, Casper C -- Kapitein, Lukas C -- England -- Nature. 2015 Feb 5;518(7537):111-4. doi: 10.1038/nature14128. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25561173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology/radiation effects ; Biological Transport/radiation effects ; Cell Compartmentation/*physiology/radiation effects ; Cells, Cultured ; Cytoskeleton/metabolism/radiation effects ; Dendritic Spines/metabolism/radiation effects ; Dyneins/metabolism/radiation effects ; Endosomes/*metabolism/radiation effects ; Hippocampus/cytology ; Intracellular Space/metabolism/radiation effects ; Kinesin/metabolism/radiation effects ; Microtubules/metabolism/radiation effects ; Mitochondria/*metabolism/radiation effects ; Myosin Type V/metabolism/radiation effects ; Optogenetics/*methods ; Peroxisomes/*metabolism/radiation effects ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Axon extension occurs independently of centrosomal microtubule nucleation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-09
    Description: Microtubules are polymeric protein structures and components of the cytoskeleton. Their dynamic polymerization is important for diverse cellular functions. The centrosome is the classical site of microtubule nucleation and is thought to be essential for axon growth and neuronal differentiation--processes that require microtubule assembly. We found that the centrosome loses its function as a microtubule organizing center during development of rodent hippocampal neurons. Axons still extended and regenerated through acentrosomal microtubule nucleation, and axons continued to grow after laser ablation of the centrosome in early neuronal development. Thus, decentralized microtubule assembly enables axon extension and regeneration, and, after axon initiation, acentrosomal microtubule nucleation arranges the cytoskeleton, which is the source of the sophisticated morphology of neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stiess, Michael -- Maghelli, Nicola -- Kapitein, Lukas C -- Gomis-Ruth, Susana -- Wilsch-Brauninger, Michaela -- Hoogenraad, Casper C -- Tolic-Norrelykke, Iva M -- Bradke, Frank -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):704-7. doi: 10.1126/science.1182179. Epub 2010 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Independent Junior Research Group Axonal Growth and Regeneration, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20056854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/metabolism ; Axons/*physiology/ultrastructure ; Axotomy ; Centrosome/*physiology/ultrastructure ; Hippocampus/*cytology ; Mice ; Microtubule-Associated Proteins/metabolism ; Microtubules/*metabolism/ultrastructure ; Nerve Regeneration ; Neurogenesis ; Neurons/*physiology/ultrastructure ; Rats ; Tubulin/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-01-29
    Description: Hypertrophic scarring and poor intrinsic axon growth capacity constitute major obstacles for spinal cord repair. These processes are tightly regulated by microtubule dynamics. Here, moderate microtubule stabilization decreased scar formation after spinal cord injury in rodents through various cellular mechanisms, including dampening of transforming growth factor-beta signaling. It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth-competent sensory neurons. Microtubule stabilization also promoted growth of central nervous system axons of the Raphe-spinal tract and led to functional improvement. Thus, microtubule stabilization reduces fibrotic scarring and enhances the capacity of axons to grow.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330754/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330754/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hellal, Farida -- Hurtado, Andres -- Ruschel, Jorg -- Flynn, Kevin C -- Laskowski, Claudia J -- Umlauf, Martina -- Kapitein, Lukas C -- Strikis, Dinara -- Lemmon, Vance -- Bixby, John -- Hoogenraad, Casper C -- Bradke, Frank -- R01 HD057632/HD/NICHD NIH HHS/ -- R01 HD057632-04/HD/NICHD NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- R01 NS059866-03/NS/NINDS NIH HHS/ -- R01 NS059866-04/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Feb 18;331(6019):928-31. doi: 10.1126/science.1201148. Epub 2011 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Axonal Growth and Regeneration Group, Max Planck Institute of Neurobiology, Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21273450" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Cells, Cultured ; Chondroitin Sulfate Proteoglycans/metabolism ; Cicatrix/pathology/*prevention & control ; Female ; Ganglia, Spinal/cytology ; Kinesin/metabolism ; Microtubules/drug effects/*metabolism ; Paclitaxel/*administration & dosage/pharmacology ; Protein Transport ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells/physiology ; Signal Transduction ; Smad2 Protein/metabolism ; Spinal Cord/cytology/drug effects ; Spinal Cord Injuries/*drug therapy/pathology/*physiopathology ; *Spinal Cord Regeneration ; Transforming Growth Factor beta/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    End-binding proteins sensitize microtubules to the action of microtubule-targeting agents (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-05-14
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    EBs sensitize microtubules to drug action [Biochemistry] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-05-29
    Description: Microtubule-targeting agents (MTAs) are widely used for treatment of cancer and other diseases, and a detailed understanding of the mechanism of their action is important for the development of improved microtubule-directed therapies. Although there is a large body of data on the interactions of different MTAs with purified tubulin and...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Exploring cytoskeletal diversity in neurons (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-07-20
    Keywords: Cell Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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