Biology subjects

Fuerst, D.

Publications and source records attributed to Fuerst, D..

4 recordsLinked to original sources

bioRxiv2024

Transposable elements are entangled in rapid adaptation to climate change

Biodiversity conservation is urged at biodiversity hotspots that are under constant threat from anthropogenic development, yet a careful examination of the adaptive potential is a prerequisite for action. The Levant is considered a biodiversity hotspot and the distribution edge for many species, including important crop wild relatives. This region is under accelerated desertification and constantly disturbed by human activities, thus urging intervenient action. We collected and sequenced 300 wild barley plants along an eco-geographic gradient following a unique ecological-genetic sampling design. This scheme enabled to overcome the tight correlation between environmental and geographic distances. Phenotypic data was collected from 3600 progeny plants over three years and enabled to identify adaptive haplotype blocks comprised of phenological regulating genes tightly linked to drought and heat responsive genes. These haplotype blocks were highly enriched for transposable elements insertions, likely regulating genetic variation around adaptive genes, especially in stressed populations. Ecological and evolutionary models using over 2600 observations were combined to predict maladaptive risk, indicating that populations will be funneled into higher water availability refugia habitats while increasing isolation. Our findings highlight the main factors affecting rapid local adaptation and provide important recommendations for biodiversity management and conservation.

plant biology↗

bioRxiv2024

Cardiac stress leads to regulation of Filamin C dimerisation via an ancient phosphorylation-modulated interaction with HSPB7

The biomechanical properties and responses of tissues underpin a variety of physiological functions and pathologies. In striated muscle, the actin-binding protein filamin C (FLNC) is a key protein whose variants causative for a wide range of cardiomyopathies and musculoskeletal pathologies. Seemingly a multi-functional protein that interacts with a variety of partners, how FLNC is regulated at the molecular level is not well understood. Here we have investigated its interaction with HSPB7, a cardiac-specific molecular chaperone whose absence is embryonically lethal. We found that FLNC and HSPB7 interact in cardiac tissue under biomechanical stress, forming a strong hetero-dimer whose structure we have solved by means of X-ray crystallography. Our quantitative analyses show that the hetero-dimer out-competes the FLNC homo-dimer interface, potentially acting to abrogate the ability of the protein to cross-link the actin cytoskeleton, and to enhance its diffusive mobility. We show that phosphorylation of FLNC at threonine 2677, located at the dimer interface and associated with cardiac stress, acts to favour the homo-dimer. Conversely, phosphorylation at tyrosine 2683, also at the dimer interface, has the opposite effect and shifts the equilibrium towards the hetero-dimer. Evolutionary analysis and ancestral sequence reconstruction reveals this interaction and its mechanisms of regulation to date around the time primitive hearts evolved in chordates. Our work rationalises on the molecular level how FLNC might switch between stabilising functions in the cell, and reveals how HSPB7 acts as a specific molecular chaperone that regulates FLNC.

molecular biology↗

bioRxiv2021

Decoupling the molecular regulation of perenniality and flowering in bulbous barley (Hordeum bulbosum)

Global crop production is being challenged by rapid population growth, declining natural resources, and dramatic climatic turnovers. These challenges have prompted plant breeders to explore new ventures to enhance adaptation and sustainability in crops. One intriguing approach to make agriculture more sustainable is by turning annual systems into perennial which offers many economic and biodiversity-friendly benefits. Previous attempts to develop a perennial cereal crop employed a classical breeding approach and extended over a long period with limited success. Thus, elucidating the genetic basis of perenniality at the molecular level can accelerate the breeding process. Here, we investigated the genetic basis of bulb formation in the barley congener species Hordeum bulbosum by elucidating the transcripts presence/absence variation compared with other annual species in the Poaceae, and a differential expression analysis of meristem tissues. The PAV analysis recaptured the expected phylogeny and indicated that H. bulbosum is enriched with developmental and disease responsive genes that are absent among annual species. Next, the abundance of transcripts was quantified and allowed to identify differentially expressed genes that are associated with bulb formation pathways in addition to major circadian clock genes that regulate flowering. A first model for the bulb formation pathway is suggested and include developmental and starch biosynthesis genes. To the best of our knowledge this is the first transcriptome developed for H. bulbosum and the first attempt to describe the regulation of bulb initiation in cereals at the molecular level.

plant biology↗

bioRxiv2018

Phosphorylation of HspB1 regulates its mechanosensitive molecular chaperone interaction with native filamin C

Small heat-shock proteins (sHsps; HspBs) are molecular chaperones involved in the cellular stress response and a range of basal functions. Despite a multitude of targets, sHsp interactions are not well understood due their heterogeneous structures and weak binding affinities. The most widely expressed human sHsp, HspB1, is prevalent in striated muscle, where the actin cross-linker filamin C (FLNC, {gamma}-filamin, ABP-L) is a putative binding partner. Musculoskeletal HspB1 is phosphorylated in response to a variety of cues, including mechanical stress, which promotes oligomer disassembly and association with myoarchitectural elements. Here, we report the up-regulation and interaction of both proteins in the hearts of a mouse model of heart failure, with HspB1 being phosphorylated and FLNC increasingly associated with the sarcomeric Z-disc. We used a combination of structural approaches to reveal that phosphorylation of HspB1 results in increased availability of the residues surrounding the phosphosite, facilitating their interaction with folded FLNC domains equivalent to a force-sensing region in the paralog filamin A. By employing native mass spectrometry, we show that domains 18 to 21 of FLNC are extensible under conditions mimicking force, with phosphorylated HspB1 stabilising an intermediate from further unfolding. These findings report on conformations accessible during the cycles of mechanical extension central to filamin function, and are consistent with an interaction between the chaperone and a native target that is strengthened upon the application of force. This may represent a new mode of molecular chaperone activity, allowing HspB1 to protect FLNC from over-extension during mechanical stress.

biophysics↗