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	Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS.
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	26(39),pp.10006-19
著者・共著者	Yuan Aidong, Rao Mala V, Sasaki Takahiro, Chen Yuanxin, Kumar Asok, Veeranna, Liem Ronald K H, Eyer Joel, Peterson Alan C, Julien Jean-Pierre, Nixon Ralph A
発行年月	2006/09
概要	Alpha-internexin, a neuronal intermediate filament protein implicated in neurodegenerative disease, coexists with the neurofilament (NF) triplet proteins (NF-L, NF-M, and NF-H) but has an unknown function. The earlier peak expression of alpha-internexin than the triplet during brain development and its ability to form homopolymers, unlike the triplet, which are obligate heteropolymers, have supported a widely held view that alpha-internexin and neurofilament triplet form separate filament systems. Here, we demonstrate, however, that despite a postnatal decline in expression, alpha-internexin is as abundant as the triplet in the adult CNS and exists in a relatively fixed stoichiometry with these subunits. Alpha-internexin exhibits transport and turnover rates identical to those of triplet proteins in optic axons and colocalizes with NF-M on single neurofilaments by immunogold electron microscopy. Alpha-internexin also coassembles with all three neurofilament proteins into a single network of filaments in quadruple-transfected SW13vim(-) cells. Genetically deleting NF-M alone or together with NF-H in mice dramatically reduces alpha-internexin transport and content in axons throughout the CNS. Moreover, deleting alpha-internexin potentiates the effects of NF-M deletion on NF-H and NF-L transport. Finally, overexpressing a NF-H-LacZ fusion protein in mice induces alpha-internexin and neurofilament triplet to aggregate in neuronal perikarya and greatly reduces their transport and content selectively in axons. Our data show that alpha-internexin and the neurofilament proteins are functionally interdependent. The results strongly support the view that alpha-internexin is a fourth subunit of neurofilaments in the adult CNS, providing a basis for its close relationship with neurofilaments in CNS diseases associated with neurofilament accumulation.
DOI	10.1523/JNEUROSCI.2580-06.2006
PMID	17005864