English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/130177
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis

AutorAsencio, Claudio ; Santarella-Mellwig, Rachel; Gorjánácz, Mátyás
Fecha de publicación2013
Citación4th Spanish Worm Meeting (2013)
ResumenThe nuclear envelope (NE) comprises inner and outer nuclear membranes that fuse at nuclear pore complexes. In metazoa the NE is broken down upon entry into mitosis and reformed upon mitotic exit; how this happens is not fully understood. The LEM domain protein family shares a ~40 amino acid domain, first identified in the proteins Lap2, Emerin and Man1. Most LEM proteins contain transmembrane domains, reside in the INM and interact with the nuclear lamina. One described function of the LEM domain is to interact with the essential and highly conserved chromatin-binding protein Barrier-to-autointegration factor (BAF). These BAF-LEM interactions serve as an important link between chromatin and the NE, both through the maintenance of nuclear architecture and during post-mitotic NE reassembly. Numerous studies have shown that NE breakdown (NEBD) and reformation are controlled by protein phosphorylation. Members of the Vaccinia-Related Kinase (VRK) family of mitotic kinases phosphorylate BAF in mitosis and meiosis; this modification strongly reduces the affinity of BAF for chromatin and slightly weakens its affinity for LEM proteins. Phosphorylation of BAF by VRK-1 is therefore proposed to be essential to break the link between chromatin, BAF and LEM proteins upon entry into mitosis. However the mechanism that permits BAF re-association with chromatin upon mitotic exit is unclear. Protein phosphatases regulate numerous processes during mitotic progression but their roles in mitotic exit are largely uncharacterized. A protein phosphatase 2A complex comprising PP2A-CA, PP2A-R1A and PP2A-B55α has been shown to regulate mitotic exit in human cells, although the target(s) of this complex are unknown. Here we show that a PP2A complex regulates BAF chromatin recruitment during mitotic exit and is required to enable BAFʼs essential function in NE assembly. In addition, we show that the uncharacterized LEM protein Lem4 is essential for BAF recruitment to chromatin upon mitotic exit in C. elegans and human cells. Lem4 depletion or mutation causes NE morphology defects and BAF hyperphosphorylation. In vivo and in vitro data show that BAF phosphorylation is dependent on VRK-1 and is counteracted by protein phosphatase 2A (PP2A). We propose an evolutionarily conserved model whereby Lem4 coordinates the control of BAF dephosphorylation by interacting with and inhibiting VRK-1 and recruiting a PP2A complex to BAF. This results in BAF dephosphorylation and chromatin recruitment, thereby facilitating NE assembly during mitotic exit.
DescripciónResumen del trabajo presentado al 4th Spanish Worm Meeting, celebrado en Carmona (Sevilla) del 14 al 15 de marzo de 2013.-- et al.
Aparece en las colecciones: (CABD) Comunicaciones congresos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Mostrar el registro completo

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.