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Leschziner, A.

Publications and source records attributed to Leschziner, A..

2 recordsLinked to original sources

The LOTUS domain of Oskar promotes localisation of both protein and mRNA components of Drosophila germ plasm

Germ cells transmit genetic information to the next generation in multicellular organisms. In Drosophila melanogaster, germ cells are determined by germ plasm, a specialised cytoplasm assembled by the Oskar protein. The current view of the molecular mechanism of germ plasm assembly attributes recruitment of protein and mRNA germ plasm components to distinct domains of the Oskar protein, called the LOTUS and OSK domains respectively. However, most evidence for this model is based on in vitro studies. Here we test the ability of Oskar variants to assemble functional germ plasm in vivo. We found that Vasa recruitment was largely unperturbed by LOTUS deletion or mutations in vivo. In contrast, nanos and pgc mRNA recruitment was affected by LOTUS domain perturbations, despite the current model attributing mRNA recruitment to the distinct OSK domain. Taken together, these data suggest a revision of the prevailing modular view of Oskars structure-function mechanism.

developmental biology↗

Cryo-EM visualizes multiple steps of dynein activation pathway

Cytoplasmic dynein-1 (dynein) is an essential molecular motor controlled in part by autoinhibition. We recently identified a structure of partially autoinhibited dynein bound to Lis1, a key dynein regulator mutated in the neurodevelopmental disease lissencephaly. This structure provides an intermediate state in dyneins activation pathway; however, other structural information is needed to fully explain Lis1 function in dynein activation. Here, we used cryo-EM and samples incubated with ATP for different times to reveal novel conformations that we propose represent intermediate states in the dyneins activation pathway. We solved sixteen high-resolution structures, including seven distinct dynein and dynein-Lis1 structures from the same sample. Our data also support a model in which Lis1 relieves dynein autoinhibition by increasing its basal ATP hydrolysis rate and promoting conformations compatible with complex assembly and motility. Together, this analysis advances our understanding of dynein activation and the contribution of Lis1 to this process.

biophysics↗