ササキ　タカヒロ   Sasaki Takahiro   佐々木　孝寛    所属   医学部 医学科（東京女子医科大学病院）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Neurofilaments form a highly stable stationary cytoskeleton after reaching a critical level in axons.
掲載誌名	正式名：The Journal of neuroscience : the official journal of the Society for Neuroscience 略　 称：J Neurosci ISSNコード：15292401/02706474
掲載区分	国外
巻・号・頁	29(36),pp.11316-29
著者・共著者	Yuan Aidong†, Sasaki Takahiro†, Rao Mala V, Kumar Asok, Kanumuri Vivek, Dunlop David S, Liem Ronald K, Nixon Ralph A
担当区分	筆頭著者
発行年月	2009/09
概要	The ultrastructural view of the axonal cytoskeleton as an extensively cross-linked network of neurofilaments (NFs) and other cytoskeletal polymers contrasts with the dynamic view suggested by axonal transport studies on cytoskeletal elements. Here we reconcile these perspectives by showing that neurons form a large NF network along axons which is unequivocally stationary, metabolically stable, and maintained by NFs and nonfilamentous subunit assemblies undergoing slow transport by intermittent rapid movements and pauses. In mouse primary cortical neurons transfected with EGFP-NFL, formation of this stationary NF network requires a critical level of NFs, which explains its absence in NF-poor developing neurons studied previously. Most NFs at proximal axon regions were in a stationary structure coexisting with a smaller pool of moving EGFP-NFL assemblies that were mainly nonfilamentous. Distally along the same axon, EGFP-labeled NFL was much less abundant, and we detected only short filaments moving bidirectionally by slow transport (rapid movements and pauses) as previously described. In living mice, >25% of radiolabeled newly synthesized NFs remained in optic axons after slowly transported NFs had exited. Retained NF remained fixed over several months in a nonuniform distribution and exhibited exceptionally slow turnover (t(1/2) >2.5 months), implying that, at steady state, >90% of NFs in mature optic axons comprise the stationary cytoskeleton and <10% are undergoing slow transport. These findings reconcile in vitro and in vivo axonal transport observations, showing that slowly transported NFs or subunit oligomers are precursors to a highly stable stationary cytoskeletal network that supports mature axons.
DOI	10.1523/JNEUROSCI.1942-09.2009
PMID	19741138