Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins |
| |
Authors: | Duband-Goulet Isabelle Woerner Stephanie Gasparini Sylvaine Attanda Wikayatou Kondé Emilie Tellier-Lebègue Carine Craescu Constantin T Gombault Aurélie Roussel Pascal Vadrot Nathalie Vicart Patrick Ostlund Cecilia Worman Howard J Zinn-Justin Sophie Buendia Brigitte |
| |
Institution: | aLaboratoire du Stress et Pathologies du Cytosquelette, Université Paris Diderot-Paris 7, CNRS, Institut de Biologie Fonctionnelle et Adaptative, 4 rue M.A. Lagroua Weill Halle, 75205 Paris cedex 13, France;bLaboratoire de Biologie Structurale et Radiobiologie, URA CNRS 2096, Commissariat à l'Energie Atomique Saclay, 91190 Gif-sur-Yvette, France;cINSERM U759, Institut Curie/Université de Paris-Sud, 91405 Orsay Cedex, France;dInstitut Jacques Monod, UMR 7592, Université Paris Diderot-Paris 7, CNRS, 15 rue Helene Brion, 75205 Paris, France;eDepartment of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA |
| |
Abstract: | 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 (?607–656) 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. |
| |
Keywords: | Lamin SREBP1 Nuclear envelope Lipodystrophy Progeria |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|