Some molecules have a single, highly specific function in physiology, while others have a much broader remit. Kinases in the IKK (inhibitor of nuclear factor êB (NF-êB) kinase) family are of the latter sort, playing a variety of roles in the immune system, cancer, and differentiation. Previous work with a related kinase, IKKå, in Drosophila has shown that this protein regulates the cytoskeleton and cell elongation in a number of contexts. It has yet to be shown, however, how it accomplishes this.
Activated IKKå (Magenta) accumulates at the tips of growing bristles, and actin bundles (green) run along the long axis of growing bristles.
A new report by Tetsuhisa Otani in the Laboratory of Morphogenetic Signaling (Shigeo Hayashi, Group Director) and colleagues, working in collaboration with the CDB Electron Microscope and Proteomics labs, does just that. In an article published in Developmental Cell, the groups show that this factor regulates shuttling of endosomes in the tips of growing mechanosensory bristles, converting the direction of their trafficking from incoming to outward bound.
Bristles form from single cells during the fly’s pupal stage. A previous report had indicated that IKKå is expressed at the tips of these structures. Otani looked at the active, phosphorylated form of the molecule and found that it indeed accumulated at the tips of growing bristles. He looked closer at cytoskeletal organization in these structures in wildtype and IKKå mutants, and found that in the mutant bristles, actin bundles were poorly organized and frequently had failed to attach to their anchor points in the cell cortex. Transmission electron microscopy further showed that while microtubules in mutants maintained their usual orientation with the respect to the bristle, an abnormal number of vesicles had accumulated in this space, suggesting that vesicle transport was somehow affected.
An examination of vesicle markers turned up a promising candidate in Rab11, a recycling endosome protein known to be essential in bristle morphogenesis. In contrast to its tendency to cluster around the tip in control animals, Rab11 was clumped in the bristle shaft in IKKå mutants. Other endosome markers also showed aberrant localization. The effect was replicated in cultured cells, in which mutant IKKå caused Rab11 to aggregate.
What then was the link between the defects in actin bundles and endosome distribution in IKKå mutants? Looking at the timing of these events, Otani found that Rab11 accumulation precedes the misrouting of actin, and was unaffected by various mutations that disturb the bundling of actin filaments, suggesting that IKKå’s roles in Rab11 distribution and actin bundling are independent.
He next used photobleaching and time-lapse imaging to track the localization of Rab11 over time. Rab11 normally moves along the bristle, shuttling between shaft and tip in a state of dynamic equilibrium. This rate and overall directionality of this back-and-forth varied, and was at its highest during bristle elongation. Looking for a mechanism, the group examined functional relationships between IKKå, Rab11, and the Rab11 effector, Nuf, which binds to Rab11 and the Dynein light intermediate chain (a component in microtubule trafficking). What they found pointed to opposing roles for IKKå and Nuf in the trafficking of Rab11. This antagonistic effect appears to be due to the phosphorylation of Nuf at a specific amino acid (serine 225) by IKKå. Preliminary experiments using IKKå homologs in mammalian cells suggested that the function of this factor in the trafficking of recycling endosomes is conserved.
"In addition to their role as vehicles for cellular materials, endosomes also serve as a platform for various signaling activities in cell proliferation and immunity,” says Hayashi. “The identification of new downstream targets of IKKå sheds light on the roles of endosomal trafficking in morphogenesis, innate immunity, and cancer."[ Contact ]
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences