Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins

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• 作者：Isabelle Duband-Goulet^a ;   ; ¹ ; Stephanie Woerner^a ;   ; ¹ ; Sylvaine Gasparini^b ; Wikayatou Attanda^a ;   ; ² ; Emilie Kondé ; ^b ; Carine Tellier-Lebè ; gue^b ; Constantin T. Craescu^c ;   ; ^&dagger ; ; Auré ; lie Gombault^a ;   ; ³ ; Pascal Roussel^d ;   ; ⁴ ; Nathalie Vadrot^a ; Patrick Vicart^a ; Cecilia Ö ; stlund^e ; Howard J. Worman^e ; Sophie Zinn-Justin^b ; Brigitte Buendia^a ;   ; ^{brigitte.buendia@univ-paris-diderot.fr}
• 关键词：Lamin ; SREBP1 ; Nuclear envelope ; Lipodystrophy ; Progeria
• 刊名：Experimental Cell Research
• 出版年：2011
• 出版时间：10 December 2011
• 年：2011
• 卷：317
• 期：20
• 页码：2800-2813
• 全文大小：1803 K

文摘

Lamins A and C are nuclear intermediate filament proteins expressed in most differentiated somatic cells. Previous data suggested that prelamin A, the lamin A precursor, accumulates in some lipodystrophy syndromes caused by mutations in the lamin A/C gene, and binds and inactivates the sterol regulatory element binding protein 1 (SREBP1). Here we show that, in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1. Such interactions also occur in HeLa cells, since expression of lamin tail regions impedes nucleolar accumulation of the SREBP1 polypeptide fused to a nucleolar localization signal sequence. In addition, the tail regions of A-type lamin variants that occur in Dunnigan-type familial partial lipodystrophy of (R482W) and Hutchison Gilford progeria syndrome (?07?56) bind to the SREBP1 polypeptide in vitro, and the corresponding FLAG-tagged full-length lamin variants co-immunoprecipitate the SREBP1 polypeptide in cells. Overexpression of wild-type A-type lamins and variants favors SREBP1 polypeptide localization at the intranuclear periphery, suggesting its sequestration. Our data support the hypothesis that variation of A-type lamin protein level and spatial organization, in particular due to disease-linked mutations, influences the sequestration of SREBP1 at the nuclear envelope and thus contributes to the regulation of SREBP1 function.