Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification.

Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. Research Abstract Details 

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Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. Abstract Text:

Noritaka Yamaguchi,Hiroyuki Koizumi,Junken Aoki,Yumiko Natori,Kiyotaka Nishikawa,Yasuhiro Natori,Yasukazu Takanezawa,Hiroyuki Arai,

LIS1, a causative gene product for type I lissencephaly, binds to and regulates the dynein motor and the centrosome. LIS1 also forms a complex with the catalytic subunits alpha1 and alpha2 of type I platelet-activating factor acetylhydrolase [PAF-AH (I)]. However, the cellular function of the catalytic subunits remains unknown. In this study, we showed that over-expression of the catalytic subunits, especially alpha2, in cultured cells induced dramatic phenotypical changes including nuclear shape change, centrosomal amplification and microtubule disorganization. We examined if these effects were due to the catalytic activity and/or binding of alpha2 to LIS1. Substitution of a single amino acid Glu39 of murine alpha1 and alpha2 by Asp (alpha2-E39D) did not affect catalytic activity but completely abolished LIS1 binding. Over-expression of either alpha2-E39D or the catalytically inactive alpha2-S48C revealed that alpha2-E39D, but not alpha2-S48C, lost its ability to induce above-mentioned phenotypic changes. Biochemical analyses showed that LIS1 present in the precipitate fraction of murine brain homogenates could be translocated to the soluble fraction by alpha2, but not by alpha2-E39D. These results suggest that over-expression of the PAF-AH (I) catalytic subunits induces centrosomal amplification and microtubule disorganization by disturbing intracellular localization of LIS1.

Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. Publishing Authors By Initials

N Yamaguchi,H Koizumi,J Aoki,Y Natori,K Nishikawa,Y Natori,Y Takanezawa,H Arai,

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Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Genes to cells : devoted to molecular & cellular m

VOLUME: 12

Page Numbers: 1153-61

Journal Abbreviation: Genes Cells

ISSN: 1356-9597

DAY: 21

MONTH: Oct

YEAR: 2007

Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. Information

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LANGUAGE: eng

NlmUniqueID: 9607379

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Grant and Affiliation Information for Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification.

AFFILIATION: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Country: England

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MEDLINETA: Genes Cells

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