Biology subjects

Pfister, A.

Publications and source records attributed to Pfister, A..

4 recordsLinked to original sources

bioRxiv2026

A tight balance of anabolic mTORC1 signaling and catabolic autophagic activity regulates zebrafish heart regeneration

Zebrafish can regenerate the heart by proliferation of cardiomyocytes. While the innate immune response and wound re-vascularization are pre-requisites for cardiomyocyte regeneration, little is known about signals linking early injury responses with the initiations of regenerative programs in cardiomyocytes. Here we show that mTOR (mechanistic target of rapamycin) signaling is rapidly activated in response to heart injury in many cell types of the heart including endothelial cells, cardiomyocytes and macrophages, but surprisingly not in neutrophils. We find that mTORC2 regulates macrophage recruitment to the wound, while mTORC1 is required for wound debris clearance by macrophages. In addition, mTOR signaling is required for wound re-vascularization. Interestingly, it also appears to directly regulate cardiomyocyte dedifferentiation and proliferation, making mTOR signaling a central hub for regenerative responses. Anabolic mTOR signaling acts as potent inhibitor of catabolic autophagy in many systems. Yet, we observed upregulation of autophagy within border zone cardiomyocytes where mTOR signaling is active. We show that mTOR signaling limits, but does not block autophagy, and that autophagic flux is regulated by both inhibitory mTOR signaling and stimulatory JNK and MEK pathways. Our results indicate that a fine-balanced anabolic and catabolic injury response is essential for zebrafish heart regeneration. Furthermore, they reveal interesting differences in the regulation of mTOR signaling and autophagy between the regenerative zebrafish heart and non-regenerative mammalian hearts.

developmental biology↗

bioRxiv2020

Dynamic characteristics rather than static hubs are important in biological networks

Biological processes are rarely a consequence of single protein interactions but rather of complex regulatory networks. However, interaction graphs cannot adequately capture temporal changes. Among models that investigate dynamics, Boolean network models can approximate simple features of interaction graphs integrating also dynamics. Nevertheless, dynamic analyses are time-consuming and with growing number of nodes may become infeasible. Therefore, we set up a method to identify minimal sets of nodes able to determine network dynamics. This approach is able to depict dynamics without calculating exhaustively the complete network dynamics. Applying it to a variety of biological networks, we identified small sets of nodes sufficient to determine the dynamic behavior of the whole system. Further characterization of these sets showed that the majority of dynamic decision-makers were not static hubs. Our work suggests a paradigm shift unraveling a new class of nodes different from static hubs and able to determine network dynamics.

bioinformatics↗

bioRxiv2019

ROS production by localized SCHENGEN receptor module drives lignification at subcellular precision

Production of reactive-oxygen species (ROS) by NADPH oxidases (NOXs) impacts many processes in animals and plants and many plant receptor pathways involve rapid, NOX-dependent increases of ROS. Yet, their general reactivity has made it challenging to pinpoint the precise role and direct cellular targets of ROS. A well-understood ROS target in plants are lignin peroxidases in the cell wall. Lignin can be deposited with exquisite spatial control, but the underlying mechanisms have remained elusive. Here we establish a full kinase signaling relay that exerts direct, spatial control over ROS production and lignification within the cell wall. We show that polar localization of a single kinase component is crucial for pathway function. Our data indicates that an intersection of more broadly localized components allows for micrometer-scale precision of lignification and that this system is triggered through initiation of ROS production as a critical peroxidase co-substrate.

plant biology↗

bioRxiv2019

Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2.

Plants use leucine-rich repeat receptor kinases (LRR-RKs) to sense sequence diverse peptide hormones at the cell surface. A 3.0 [A] crystal structure of the LRR-RK GSO1/SGN3 regulating Casparian strip formation in the endodermis reveals a large spiral-shaped ectodomain. The domain provides a binding platform for 21 amino-acid CIF peptide ligands, which are tyrosine sulfated by the tyrosylprotein sulfotransferase TPST/SGN2. GSO1/SGN3 harbors a binding pocket for sulfotyrosine and makes extended backbone interactions with CIF2. Quantitative biochemical comparisons reveal that GSO1/SGN3 - CIF2 represents one of the strongest receptor-ligand pairs known in plants. Multiple missense mutations are required to block CIF2 binding in vitro, and GSO1/SGN3 function in vivo. Using structure-guided sequence analysis we uncover novel CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK LRR-RKs as essential co-receptor kinases required for GSO1/SGN3 and GSO2 receptor activation. 0ur work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants.\n\nSignificance StatementTwo sequence-related plant membrane receptor kinases and their shape-complementary co-receptors are shown to selectively sense members of a small family of secreted peptide hormones to control formation of an important diffusion barrier in the plant root.

plant biology↗