Toll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its... Show moreToll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2-deficient (tlr2-/-) zebrafish using state-of-the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2-/- zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain-wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2-/- zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2-/- compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases. Show less
Paus, L.V. de; Yu, A.; Janssen, A.P.A.; Berg, R.J.B.H.N. van den; Heitman, L.H.; Stelt, M. van der 2024
The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor... Show moreThe cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI-121 that stabilized the inactive conformation of the CB2R. Here, we report the structure-based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click-chemistry with fluorophore-azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function. Show less
Pol, R.W.I. van der; Brinkmann, B.W.; Sevink, G.J.A. 2024
Light is required for photosynthesis, but plants are often exposed to excess light, which can lead to photodamage and eventually cell death. To prevent this, they evolved photoprotective feedback... Show moreLight is required for photosynthesis, but plants are often exposed to excess light, which can lead to photodamage and eventually cell death. To prevent this, they evolved photoprotective feedback mechanisms that regulate photosynthesis and trigger processes that dissipate light energy as heat, called non-photochemical quenching (NPQ). In excess light conditions, the light reaction and activity of Photosystem II (PSII) generates acidification of the thylakoid lumen, which is sensed by special pH-sensitive proteins called Photosystem II Subunit S (PsbS), actuating a photoprotective "switch" in the light-harvesting antenna. Despite its central role in regulating photosynthetic energy conversion, the molecular mechanism of PsbS as well as its interaction with partner proteins are not well understood. This review summarizes the current knowledge on the molecular structure and mechanistic aspects of the light-stress sensor PsbS and addresses open questions and challenges in the field regarding a full understanding of its functional mechanism and role in NPQ. Show less
Kim Y.; Alia, A.; Kurle-Tucholski, P.; Wiebeler, C.; Matysik, J. 2024
