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 ]
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy