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The nuclear envelope protein LEM-2 is critical for nuclear positioning and centrosome attachment

AutorMorales-Martínez, Adela ; Ayuso, Cristina ; Askjaer, Peter
Fecha de publicación2013
Citación4th Spanish Worm Meeting (2013)
ResumenLEM domain proteins (for LBR, Emerin and MAN1) are typically localized in the inner nuclear membrane where they serve as bridging molecules between the nuclear membranes, the nuclear lamina and chromatin proteins, such as BAF. In addition, LEM domain proteins regulate gene expression through specific interaction with transcription factors and chromatin modifying enzymes at the nuclear envelope. Mutations in LEM domain proteins or in interacting nuclear envelope proteins cause a wide range of severe human diseases, collectively known as laminopathies. Most laminopathies are still poorly understood and no efficient treatment has been identified. To explore the mechanisms behind LEM domain protein activities we are characterizing the C. elegans lem-2 gene, which encodes a protein homologous to vertebrate inner nuclear membrane proteins LEM2 and MAN1. Previous experiments have reported that LEM-2 shares redundant roles with emerin/EMR-1. We find that LEM-2 is expressed in all cell types but is enriched in the germ line and intestine relative to EMR-1. Moreover, LEM-2 is recruited significantly earlier than EMR-1 during nuclear envelope reassembly in telophase, suggesting that LEM-2 carries specific functions. Indeed, live imaging reveals that nuclear morphology is irregular in embryos lacking expression of LEM-2 and EMR-1 protein turnover is accelerated in lem-2 adults. The nuclear envelope is responsible for nucleus-centrosome attachment and alterations in the nuclear envelope can cause abnormal nuclear and centrosome positioning. In C. elegans nuclear positioning is mainly studied in mid-stage embryos and early larvae but we observe that mutation of lem-2 causes defects already in the second embryonic division. During AB division nuclei separate slower than in wild type embryos and nucleating centrosomes are observed at abnormal distance from nuclei. Thus, although expressed in the inner nuclear membrane our data suggest that LEM-2 is involved in the anchoring of centrosomes to the outer nuclear membrane. To identify potential interaction partners in this process, we are performing a genome-wide RNAi screen for enhancers of lem-2 phenotypes.
DescripciónResumen del trabajo presentado al 4th Spanish Worm Meeting, celebrado en Carmona (Sevilla) del 14 al 15 de marzo de 2013.
URIhttp://hdl.handle.net/10261/130074
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