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Biology subjects

Mischke, S.

Publications and source records attributed to Mischke, S..

3 recordsLinked to original sources

Tibetan terrestrial and aquatic ecosystems collapsed with cryosphere loss inferred from sedimentary ancient metagenomics

Glacier and permafrost shrinkage and land-use intensification threaten diverse mountain wildlife and affect nature conservation strategy. Our understanding of alpine ecological dynamics is, however, insufficient because time series portraying ecosystem complexity adequately are missing. Here, we present an ancient metagenomic record tracing 317 terrestrial and aquatic taxa, including mammals, fish, plants, and microorganisms retrieved from a lake sediment core from the southeastern Tibetan Plateau covering the last 18,000 years. We infer that steppe-meadow turned into woodland at 14 ka (cal BP) controlled by warming-induced cryosphere loss, further driving a change of herbivore dominance from wild yak to deer. Network analyses reveal that root hemiparasitic and cushion plants are keystone taxa, likely altering the terrestrial ecosystem via facilitation. These findings refute the hypothesis of top-down control by large herbivores in the alpine ecosystem. We also find that glacier mass loss significantly contributes to considerable turnover in the aquatic community at 14 ka, transitioning from glacier-related (blue-green) algae to abundant non-glacier-preferring picocyanobacteria, macrophytes, fish, and fish-eating otters. Human impact contributes little to shaping the alpine ecosystems. By applying network analysis, we provide the first sedaDNA-based assessment of the stress-gradient hypothesis. As cryosphere loss is ongoing due to climate warming, prioritizing the protection of habitats with rich nurse plants that aid neighbors in adapting to stressful conditions is likely to be a more beneficial conservation measure than livestock reduction in the Tibetan Plateau. Significance statementMerging ancient metagenomics and network analysis gives new insights into conserving the Tibetan alpine ecosystem under ongoing warming and human perturbations. We investigated the assembly of the Yak steppe-meadow ecosystem and an alpine lake system in response to cryosphere changes over the past [~]18,000 years on the Tibetan Plateau. Large herbivores cannot be a cost-effective natural climate solution to stabilize the Tibetan alpine ecosystem because they are not keystone taxa at the ecosystem scale. Furthermore, there is no support that land use considerably shapes the alpine communities and ecosystems. Protection policy should thus prioritize focus on alpine areas with intense land use and rich in root hemiparasitic and cushion plants because these taxa act as facilitators in the ecosystem.

ecology↗

The deubiquitylase USP9X controls ribosomal stalling

When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases respectively, through ubiquitylation of the eS10 and uS10 sub-units of the ribosome. It is common for the stability of RING E3 ligases to be regulated by an interacting deubiquitylase (DUB), which often opposes auto-ubiquitylation of the E3. Here, we show that the DUB USP9X directly interacts with ZNF598 and regulates its abundance through the control of protein stability in human cells. We have developed a highly specific small molecule inhibitor of USP9X. Proteomics analysis, following inhibitor treatment of HCT116 cells, confirms previous reports linking USP9X with centrosome associated protein stability and reveals loss of ZNF598 and Makorin 2. In the absence of USP9X or following chemical inhibition of its catalytic activity, steady state levels of Makorins and ZNF598 are diminished and the ribosomal quality control pathway is impaired.

cell biology↗

Measurements of the timescale and conformational space of AMPA receptor desensitization

Ionotropic glutamate receptors (iGluRs) are ligand gated ion channels that mediate excitatory synaptic transmission in the central nervous system (CNS). Desensitization of the AMPA-subtype following glutamate binding appears critical for brain function, and involves rearrangement of the ligand binding domains (LBDs). Recently, several full-length structures of iGluRs in putative desensitized states were published. These structures indicate movements of the LBDs that might be trapped by cysteine crosslinks and metal bridges. We found that cysteine mutants at the interface between subunits A and C, and lateral zinc bridges (between subunits C & D or A & B) can trap freely-desensitizing receptors in a spectrum of states with different stabilities. Consistent with close approach of subunits during desensitization processes, introduction of bulky amino acids at the A-C interface produced a receptor with slow recovery from desensitization. Further, in wild-type GluA2 receptors, we detected population of stable desensitized state with a lifetime around 1 second. Using mutations that progressively stabilise deep desensitize states (E713T & Y768R), we were able to selectively protect receptors from crosslinks at both the diagonal and lateral interfaces. Ultrafast perfusion enabled us to perform chemical modification in less than 10 ms, reporting movements associated to desensitization on this timescale within LBD dimers in resting receptors. These observations suggest small disruptions of quaternary structure are sufficient for fast desensitization, and that substantial rearrangements likely correspond to stable desensitized states that are adopted relatively slowly, on a timescale much longer than physiological receptor activation. Significance statementiGluRs are central components of fast synaptic transmission in the brain. iGluR desensitization occurs as a natural consequence of receptor activation and can reduce the response of an excitatory synapse. AMPA receptor desensitization also appears necessary for proper brain development. Molecular structures of iGluRs in putative desensitized states predict a range of movements during desensitization. In the present study, we performed a series of crosslinking experiments on mutant receptors that we subjected to similar desensitizing conditions over time periods from milliseconds to minutes. These experiments allowed us to count desensitized configurations and rank them according to their stabilities. These data show that large-scale rearrangements occur during long glutamate exposures that are probably not seen in healthy brain tissue, whereas smaller changes in structure probably suffice for desensitization at synapses.

biophysics↗