Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

One third of all genes of various organisms encode membrane proteins, emphasizing their crucial cellular role. However, due to their high hydrophobicity, membrane proteins demonstrate low solubility and a high tendency for aggregation. Indeed, conventional two-dimensional gel electrophoresis (2-DE), a powerful electrophoretic method for the separation of complex protein samples that applies isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in the second dimension, has a strong bias against membrane proteins. This review describes two-dimensional electrophoretic techniques that can be used to separate membrane proteins. Alternative methods for performing conventional 2-DE are highlighted; these involve replacing the IEF with electrophoresis using cationic detergents, namely 16-benzyldimethyl-n-hexadecylammonium chloride (16-BAC) and cetyl trimethyl ammonium bromide (CTAB), or the anionic detergent SDS. Finally, the separation of native membrane protein complexes through the application of blue and clear native gel electrophoresis (BN/CN-PAGE) is reviewed, as well as the free-flow electrophoresis (FFE) of membranes.

Proteomic analyses, literature mining, and structural data were combined to generate an extensive signaling network linked to the visual G protein-coupled receptor rhodopsin. Network analysis suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking.

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Der 21. Band des "E.T.A. Hoffmann-Jahrbuchs" enthält Aufsätze über einzelne Werke Hoffmanns: In den Blick genommen wird die "Nachricht von einem gebildeten jungen Mann" mit einer neuen Sicht des Affen Milo, aus editionsphilologischer Sicht geht es um den "Ritter Gluck", thematisiert werden die intertextuellen Bezüge des Nachtstücks "Ignaz Denner" sowie Fragen von Künstlertum und Katzenleben im "Kater Murr". Ein Beitrag würdigt das bildkünstlerische Werk Hoffmanns. Der Abdruck der zeitgenössischen Rezensionen über Hoffmanns Werke wird fortgesetzt. Einem umfangreichen Besprechungsteil folgen Mitteilungen der E.T.A. Hoffmann-Gesellschaft, u.a. mit Berichten über die Hoffmann-Pflege in Kaliningrad, eine Aufführung des "Tranks der Unsterblichkeit" in Erfurt, eine Ausstellung sowie die Verleihung der "E.T.A. Hoffmann-Medaille" in Bamberg.

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