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Article: Mitochondrial clustering at the vertebrate neuromuscular junction during presynaptic differentiation

TitleMitochondrial clustering at the vertebrate neuromuscular junction during presynaptic differentiation
Authors
KeywordsNeuromuscular junction
Synaptogenesis
Presynaptic differentiation
Mitochondria
Synaptic vesicle
Cytoskeleton
Issue Date2006
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/31737
Citation
Journal of Neurobiology, 2006, v. 66 n. 6, p. 522-536 How to Cite?
AbstractDuring vertebrate neuromuscular junction (NMJ) development, presynaptic motor axons differentiate into nerve termini enriched in synaptic vesicles (SVs). At the nerve terminal, mitochondria are also concentrated, but how mitochondria become localized at these specialized domains is poorly understood. This process was studied in cultured Xenopus spinal neurons with mitochondrion-specific probe MitoTracker and SV markers. In nerve-muscle cocultures, mitochondria were concentrated stably at sites where neurites and muscle cells formed NMJs, and mitochondria coclustered with SVs where neurites were focally stimulated by beads coated with growth factors. Labeling with a mitochondrial membrane potential-dependent probe JC-1 revealed that these synaptic mitochondria were with higher membrane potential than the extrasynaptic ones. At early stages of bead-stimulation, actin-based protrusions and microtubule fragmentation were observed in neurites at bead contact sites, suggesting the involvement of cytoskeletal dynamics and rearrangement during presynaptic differentiation. Treating the cultures with an actin polymerization blocker, latrunculin A (Ltn A), almost completely abolished the formation of actin-based protrusions and partially inhibited bead-induced mitochondrial and SV clustering, whereas the microtubule disrupting agent nocodazole was ineffective in inhibiting the clustering of mitochondria and SVs. Lastly, in contrast to Ltn A, which blocked bead-induced clustering of both mitochondria and SVs, the ser/thr phosphatase inhibitor okadaic acid inhibited SV clustering but not mitochondrial clustering. These results suggest that at developing NMJs, synaptogenic stimuli induce the clustering of mitochondria together with SVs at presynaptic terminals in an actin cytoskeleton-dependent manner and involving different intracellular signaling molecules.
Persistent Identifierhttp://hdl.handle.net/10722/225408
ISSN
2008 Impact Factor: 3.84

 

DC FieldValueLanguage
dc.contributor.authorLee, CW-
dc.contributor.authorPeng, HB-
dc.date.accessioned2016-05-06T01:42:33Z-
dc.date.available2016-05-06T01:42:33Z-
dc.date.issued2006-
dc.identifier.citationJournal of Neurobiology, 2006, v. 66 n. 6, p. 522-536-
dc.identifier.issn0022-3034-
dc.identifier.urihttp://hdl.handle.net/10722/225408-
dc.description.abstractDuring vertebrate neuromuscular junction (NMJ) development, presynaptic motor axons differentiate into nerve termini enriched in synaptic vesicles (SVs). At the nerve terminal, mitochondria are also concentrated, but how mitochondria become localized at these specialized domains is poorly understood. This process was studied in cultured Xenopus spinal neurons with mitochondrion-specific probe MitoTracker and SV markers. In nerve-muscle cocultures, mitochondria were concentrated stably at sites where neurites and muscle cells formed NMJs, and mitochondria coclustered with SVs where neurites were focally stimulated by beads coated with growth factors. Labeling with a mitochondrial membrane potential-dependent probe JC-1 revealed that these synaptic mitochondria were with higher membrane potential than the extrasynaptic ones. At early stages of bead-stimulation, actin-based protrusions and microtubule fragmentation were observed in neurites at bead contact sites, suggesting the involvement of cytoskeletal dynamics and rearrangement during presynaptic differentiation. Treating the cultures with an actin polymerization blocker, latrunculin A (Ltn A), almost completely abolished the formation of actin-based protrusions and partially inhibited bead-induced mitochondrial and SV clustering, whereas the microtubule disrupting agent nocodazole was ineffective in inhibiting the clustering of mitochondria and SVs. Lastly, in contrast to Ltn A, which blocked bead-induced clustering of both mitochondria and SVs, the ser/thr phosphatase inhibitor okadaic acid inhibited SV clustering but not mitochondrial clustering. These results suggest that at developing NMJs, synaptogenic stimuli induce the clustering of mitochondria together with SVs at presynaptic terminals in an actin cytoskeleton-dependent manner and involving different intracellular signaling molecules.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/31737-
dc.relation.ispartofJournal of Neurobiology-
dc.rightsJournal of Neurobiology. Copyright © John Wiley & Sons, Inc.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.subjectNeuromuscular junction-
dc.subjectSynaptogenesis-
dc.subjectPresynaptic differentiation-
dc.subjectMitochondria-
dc.subjectSynaptic vesicle-
dc.subjectCytoskeleton-
dc.titleMitochondrial clustering at the vertebrate neuromuscular junction during presynaptic differentiation-
dc.typeArticle-
dc.identifier.emailLee, CW: chiwai.lee@hku.hk-
dc.identifier.authorityLee, CW=rp02089-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/neu.20245-
dc.identifier.pmid16555236-
dc.identifier.volume66-
dc.identifier.issue6-
dc.identifier.spage522-
dc.identifier.epage536-
dc.publisher.placeUnited States-

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