- Structure of the membrane-assembled retromer coat determined by cryo-electron tomography. [Journal Article]
- NatNature 2018 Sep 17
- Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular car...
Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes1-3. Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders4-7. How retromer is assembled and how it is recruited to form coated tubules is not known. Here we describe the structure of the retromer complex (Vps26-Vps29-Vps35) assembled on membrane tubules with the bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo-electron tomography and subtomogram averaging. This reveals a membrane-associated Vps5 array, from which arches of retromer extend away from the membrane surface. Vps35 forms the 'legs' of these arches, and Vps29 resides at the apex where it is free to interact with regulatory factors. The bases of the arches connect to each other and to Vps5 through Vps26, and the presence of the same arches on coated tubules within cells confirms their functional importance. Vps5 binds to Vps26 at a position analogous to the previously described cargo- and Snx3-binding site, which suggests the existence of distinct retromer-sorting nexin assemblies. The structure provides insight into the architecture of the coat and its mechanism of assembly, and suggests that retromer promotes tubule formation by directing the distribution of sorting nexin proteins on the membrane surface while providing a scaffold for regulatory-protein interactions.
- The role of miniaturization in the evolution of the mammalian jaw and middle ear. [Journal Article]
- NatNature 2018 Sep 17
- The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million yea...
The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million years1,2. In particular, the transformation of the mandible into a single tooth-bearing bone and the emergence of a novel jaw joint-while incorporating some of the ancestral jaw bones into the mammalian middle ear-is often cited as a classic example of the repurposing of morphological structures3,4. Although it is remarkably well-documented in the fossil record, the evolution of the mammalian jaw still poses the paradox of how the bones of the ancestral jaw joint could function both as a joint hinge for powerful load-bearing mastication and as a mandibular middle ear that was delicate enough for hearing. Here we use digital reconstructions, computational modelling and biomechanical analyses to demonstrate that the miniaturization of the early mammalian jaw was the primary driver for the transformation of the jaw joint. We show that there is no evidence for a concurrent reduction in jaw-joint stress and increase in bite force in key non-mammaliaform taxa in the cynodont-mammaliaform transition, as previously thought5-8. Although a shift in the recruitment of the jaw musculature occurred during the evolution of modern mammals, the optimization of mandibular function to increase bite force while reducing joint loads did not occur until after the emergence of the neomorphic mammalian jaw joint. This suggests that miniaturization provided a selective regime for the evolution of the mammalian jaw joint, followed by the integration of the postdentary bones into the mammalian middle ear.
- Time-asymmetric loop around an exceptional point over the full optical communications band. [Journal Article]
- NatNature 2018 Sep 17
- Topological operations around exceptional points1-8-time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching op...
Topological operations around exceptional points1-8-time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching open-system dynamics, as demonstrated in highly dissipative microwave transmission3 and cryogenic optomechanical oscillator4 experiments. In stark contrast to conventional systems based on closed-system Hermitian dynamics, environmental interferences at exceptional points are dynamically engaged with their internal coupling properties to create rotational stimuli in fictitious-parameter domains, resulting in chiral systems that exhibit various anomalous physical phenomena9-16. To achieve new wave properties and concomitant device architectures to control them, realizations of such systems in application-abundant technological areas, including communications and signal processing systems, are the next step. However, it is currently unclear whether non-Hermitian interaction schemes can be configured in robust technological platforms for further device engineering. Here we experimentally demonstrate a robust silicon photonic structure with photonic modes that transmit through time-asymmetric loops around an exceptional point in the optical domain. The proposed structure consists of two coupled silicon-channel waveguides and a slab-waveguide leakage-radiation sink that precisely control the required non-Hermitian Hamiltonian experienced by the photonic modes. The fabricated devices generate time-asymmetric light transmission over an extremely broad spectral band covering the entire optical telecommunications window (wavelengths between 1.26 and 1.675 micrometres). Thus, we take a step towards broadband on-chip optical devices based on non-Hermitian topological dynamics by using a semiconductor platform with controllable optoelectronic properties, and towards several potential practical applications, such as on-chip optical isolators and non-reciprocal mode converters. Our results further suggest the technological relevance of non-Hermitian wave dynamics in various other branches of physics, such as acoustics, condensed-matter physics and quantum mechanics.
- Sensation, movement and learning in the absence of barrel cortex. [Journal Article]
- NatNature 2018 Sep 17
- For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1-17. Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cort...
For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1-17. Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cortex in mice trained to move their large facial whiskers to detect an object by touch and respond with a lever to obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in excitatory cortical neurons. Transient optogenetic inactivation of the primary somatosensory cortex, as well as permanent lesions, initially produced both movement and sensory deficits that impaired detection behaviour, demonstrating the link between sensory and motor systems during active sensing. Unexpectedly, lesioned mice had recovered full behavioural capabilities by the subsequent session. This rapid recovery was experience-dependent, and early re-exposure to the task after lesioning facilitated recovery. Furthermore, ablation of the primary somatosensory cortex before learning did not affect task acquisition. This combined optogenetic and lesion approach suggests that manipulations of the sensory cortex may be only temporarily disruptive to other brain structures that are themselves capable of coordinating multiple, arbitrary movements with sensation. Thus, the somatosensory cortex may be dispensable for active detection of objects in the environment.
- Reducing neuronal inhibition restores locomotion in paralysed mice. [News]
- NatNature 2018; 561(7723):317-318
- Protein structures guide the design of a much-needed tool for neuroscience. [News]
- NatNature 2018; 561(7723):312-313
- Bird forecasting by radar. [News]
- NatNature 2018; 561(7723):314
- T cells engineered to home in on brain cancer. [News]
- NatNature 2018; 561(7723):319-320
- Tissue 'melting' sculpts embryo. [News]
- NatNature 2018; 561(7723):315-316
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- Forgotten heroes of the Enigma story. [News]
- NatNature 2018; 561(7723):307-308