Biology subjects

Goerlach, M.

Publications and source records attributed to Goerlach, M..

4 recordsLinked to original sources

bioRxiv2024

The Aging Synapse: An Integrated Proteomic And Transcriptomic Analysis

An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between transcriptome and proteome at soma and synaptic level during aging. Proteomic and transcriptomic data analysis reveal that, in young animals, proteins and transcripts are correlated and synaptic regulation is driven by changes in the soma. During aging, there is a decoupling between transcripts and proteins and between somatic and synaptic compartments. Furthermore, soma-synapse gradient of ribosomal genes changes upon aging, i.e. ribosomal transcripts are less abundant and ribosomal proteins are more abundant in synaptic compartment of old mice with respect to younglings. Additionally, transcriptomics data highlight a difference in the splicing of certain synaptic mRNA with aging. Taken together, our data provide a valuable resource for the study of the aging synapse.

neuroscience↗

bioRxiv2019

Structural requirements of the phytoplasma effector protein SAP54 for causing homeotic transformation of floral organs

Phytoplasmas are intracellular bacterial plant pathogens that cause devastating diseases in crops and ornamental plants by the secretion of effector proteins. One of these effector proteins, termed SECRETED ASTER YELLOWS-WITCHES BROOM PROTEIN 54 (SAP54), leads to the degradation of a specific subset of floral homeotic proteins of the MIKC-type MADS-domain family via the ubiquitin-proteasome pathway. In consequence, the developing flowers show the homeotic transformation of floral organs into vegetative leaf-like structures. The molecular mechanism of SAP54 action involves physical binding to the keratin-like K-domain of MIKC-type proteins, and to some RAD23 proteins, which translocate ubiquitylated substrates to the proteasome. The structural requirements and specificity of SAP54 function are poorly understood, however. Here we report, based on biophysical and molecular biological analyses, that SAP54 folds into -helical structures. We also show that the insertion of helix-breaking mutations disrupts correct folding of SAP54, which interferes with the ability of SAP54 to bind to its target proteins and to cause disease phenotypes in vivo. Surprisingly, dynamic light scattering data together with electrophoretic mobility shift assays suggest that SAP54 preferentially binds to multimeric complexes of MIKC-type proteins rather than to dimers or monomers of these proteins. Together with literature data this finding suggests that MIKC-type proteins and SAP54 constitute multimeric -helical coiled-coils, possibly also involving other partners such as RAD23 proteins. Our investigations clarify the structure-function relationship of an important phytoplasma effector protein and thus may ultimately help to develop treatments against some devastating plant diseases.\n\nSIGNIFICANCE STATEMENTPhytoplasmas are bacterial plant pathogens that cause devastating diseases in crops and ornamental plants by the secretion of effector proteins such as SAP54, which leads to the degradation of some floral homeotic proteins. Our study clarifies the structural requirements of SAP54 function and illuminates the molecular mode of interaction and thus may ultimately help to develop treatments against some devastating plant diseases.

plant biology↗

bioRxiv2018

Clownfishes are a genetic model of exceptional longevity and reveal molecular convergence in the evolution of lifespan

Standard evolutionary theories of aging postulate that reduced extrinsic mortality leads to evolution of longevity. Clownfishes of the genus Amphiprion live in a symbiotic relationship with sea anemones that provide protection from predation. We performed a survey and identified at least two species with lifespan of over 20 years. Given their small size and ease of captive reproduction, clownfishes lend themselves as experimental models of exceptional longevity.\n\nTo identify genetic correlates of exceptional longevity, we sequenced the transcriptomes of Amphiprion percula and A. clarkii and performed a scan for positively-selected genes (PSGs). These were compared with PSGs detected in long-lived mole rats and short-lived killifishes revealing convergent evolution in processes such as mitochondrial biogenesis. Among individual genes, the Mitochondrial Transcription Termination Factor 1 (MTERF1), was positively-selected in all three clades, whereas the Glutathione S-Transferase Kappa 1 (GSTK1) was under positive selection in two independent clades. For the latter, homology modelling strongly suggested that positive selection targeted enzymatically important residues.\n\nThese results indicate that specific pathways were recruited in independent lineages evolving an exceptionally extended or shortened lifespan and point to mito-nuclear balance as a key factor.

evolutionary biology↗

bioRxiv2017

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality

The genetic mechanisms that determine lifespan are poorly understood. Most research has been done on short lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. We obtained genomic and transcriptomic data from 17 rodent species and systematically scanned eleven lineages associated with the evolution of longevity and eusociality for positively selected genes (PSGs). The set of 319 PSGs contains regulators of mTOR and is enriched in functional terms associated with (i) processes that are regulated by the mTOR pathway, e.g. translation, autophagy and mitochondrial biogenesis, (ii) the immune system and (iii) antioxidant defense. Analyzing gene expression of PSGs during aging in the long-lived naked mole-rat and up-regulation in the short-lived rat, we found a pattern fitting the antagonistic pleiotropy theory of aging.

evolutionary biology↗