TY - JOUR A1 - Meyer, Irene A1 - Kuhnert, Oliver A1 - Gräf, Ralph T1 - Functional analyses of lissencephaly-related proteins in Dictyostelium JF - Seminars in cell & developmental biology N2 - Lissencephaly is a severe brain developmental disease in human infants, which is usually caused by mutations in either of two genes, LIS1 and DCX. These genes encode proteins interacting with both the microtubule and the actin systems. Here, we review the implications of data on Dictyostelium LIS1 for the elucidation of LIS1 function in higher cells and emphasize the role of LIS1 and nuclear envelope proteins in nuclear positioning, which is also important for coordinated cell migration during neocortical development. Furthermore, for the first time we characterize Dictyostelium DCX, the only bona fide orthologue of human DCX outside the animal kingdom. We show that DCX functionally interacts with LIS1 and that both proteins have a cytoskeleton-independent function in chemotactic signaling during development. Dictyostelium LIS1 is also required for proper attachment of the centrosome to the nucleus and, thus, nuclear positioning, where the association of these two organelles has turned out to be crucial. It involves not only dynein and dynein-associated proteins such as LIS1 but also SUN proteins of the nuclear envelope. Analyses of Dictyostelium SUN1 mutants have underscored the importance of these proteins for the linkage of centrosomes and nuclei and for the maintenance of chromatin integrity. Taken together, we show that Dictyostelium amoebae, which provide a well-established model to study the basic aspects of chemotaxis, cell migration and development, are well suited for the investigation of the molecular and cell biological basis of developmental diseases such as lissencephaly. KW - Dictyostelium KW - Lissencephaly KW - LIS1 KW - DCX KW - SUN1 KW - Centrosome Y1 - 2011 U6 - https://doi.org/10.1016/j.semcdb.2010.10.007 SN - 1084-9521 VL - 22 IS - 1 SP - 89 EP - 96 PB - Elsevier CY - London ER - TY - JOUR A1 - Samereier, Matthias A1 - Baumann, Otto A1 - Meyer, Irene A1 - Gräf, Ralph T1 - Analysis of dictyostelium TACC reveals differential interactions with CP224 and unusual dynamics of dictyostelium microtubules JF - Cellular and molecular life sciences N2 - We have localized TACC to the microtubule-nucleating centrosomal corona and to microtubule plus ends. Using RNAi we proved that Dictyostelium TACC promotes microtubule growth during interphase and mitosis. For the first time we show in vivo that both TACC and XMAP215 family proteins can be differentially localized to microtubule plus ends during interphase and mitosis and that TACC is mainly required for recruitment of an XMAP215-family protein to interphase microtubule plus ends but not for recruitment to centrosomes and kinetochores. Moreover, we have now a marker to study dynamics and behavior of microtubule plus ends in living Dictyostelium cells. In a combination of live cell imaging of microtubule plus ends and fluorescence recovery after photobleaching (FRAP) experiments of GFP-alpha-tubulin cells we show that Dictyostelium microtubules are dynamic only in the cell periphery, while they remain stable at the centrosome, which also appears to harbor a dynamic pool of tubulin dimers. KW - Dictyostelium KW - TACC KW - DdCP224 KW - XMAP215 KW - Microtubules KW - Centrosome Y1 - 2011 U6 - https://doi.org/10.1007/s00018-010-0453-0 SN - 1420-682X VL - 68 IS - 2 SP - 275 EP - 287 PB - Springer CY - Basel ER - TY - CHAP A1 - Kuhnert, Oliver A1 - Baumann, Otto A1 - Meyer, Irene A1 - Gräf, Ralph T1 - Functional characterization of CP148, a novel key component for centrosome integrity in Dictyostelium T2 - Molecular biology of the cell : the official publication of the American Society for Cell Biology Y1 - 2011 SN - 1059-1524 VL - 22 PB - American Society for Cell Biology CY - Bethesda ER -