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Unruh, J.

Publications and source records attributed to Unruh, J..

20 records · Page 2Linked to original sources

Parallel control of mechanosensory hair cell orientation by the PCP and Wnt pathways

Cell polarity plays a crucial role during development of vertebrates and invertebrates. Planar Cell Polarity (PCP) is defined as the coordinated polarity of cells within a tissue axis and is essential for processes such as gastrulation, neural tube closure or hearing. Wnt ligands can be instructive or permissive during PCP-dependent processes, and Wnt pathway mutants are often classified as PCP mutants due to the complexity and the similarities between their phenotypes. Our studies of the zebrafish sensory lateral line reveal that disruptions of the PCP and Wnt pathways have differential effects on hair cell orientations. While mutations in PCP genes cause random orientations of hair cells, mutations in Wnt pathway members induce hair cells to adopt a concentric pattern. We show that PCP signaling is normal in hair cells of Wnt pathway mutants and that the concentric hair cell phenotype is due to altered organization of the surrounding support cells. Thus, the PCP and Wnt pathways work in parallel, as separate pathways to establish proper hair cell orientation. Our data suggest that coordinated support cell organization is established during the formation of lateral line primordia, much earlier than the appearance of hair cells. Together, these finding reveal that hair cell orientation defects are not solely explained by defects in PCP signaling and that some hair cell phenotypes warrant reevaluation.

developmental biology↗

Asi1 regulates the distribution of proteins at the inner nuclear membrane in Saccharomyces cerevisiae

Inner nuclear membrane (INM) protein composition regulates nuclear function, affecting processes such as gene expression, chromosome organization, nuclear shape and stability. Mechanisms that drive changes in the INM proteome are poorly understood in part because it is difficult to definitively assay INM composition rigorously and systematically. Using a split-GFP complementation system to detect INM access, we examined the distribution of all C-terminally tagged Saccharomyces cerevisiae membrane proteins in wild-type cells and in mutants affecting protein quality control pathways, such as INM-associated degradation (INMAD), ER-associated degradation (ERAD) and vacuolar proteolysis. Deletion of the E3 ligase Asi1 had the most pronounced effect on the INM compared to mutants in vacuolar or ER-associated degradation pathways, consistent with a role for Asi1 in the INMAD pathway. Our data suggests that Asi1 not only removes mis-targeted proteins at the INM, but it also controls the levels and distribution of native INM components, such as the membrane nucleoporin Pom33. Interestingly, loss of Asi1 does not affect Pom33 protein levels but instead alters Pom33 distribution in the NE through Pom33 ubiquitination, which drives INM redistribution. Taken together, our data demonstrate that the Asi1 E3 ligase has a novel function in INM protein regulation in addition to protein turnover.

cell biology↗