Biology subjects

Kulesza, A.

Publications and source records attributed to Kulesza, A..

2 recordsLinked to original sources

bioRxiv2024

Bottom-up reconstruction of functional Death Domain Signalosomes reveals a requirement for polymer stability and avidity

A key feature of innate immune signaling is the compartmentalization of signaling effectors into cellular structures referred to as signalosomes. Critical to the formation of these compartments are protein polymers composed of Death Domains (DD). However, the biophysical properties these polymeric scaffolds require for signal transduction are not clearly defined. Here, we engineered a single-component signalosome, referred to as Chimeric Higher-order Assemblies for Receptor Mediated Signaling (CHARMS). We found that CHARMS functionality depends on the stability provided by the DD polymer, which could also be achieved with bacterial DDs and synthetic filament-forming domains. This demonstrates the importance of kinetic stability and inducibility, irrespective of the origin of the motif. By varying the multiplicity of TRAF6 interaction motifs, we demonstrate that avidity is a tunable property that can control the amplitude of signaling outputs. This work lays out a reductionist framework to dissect the required properties of signaling through polymeric scaffolds by adjusting their assembly kinetics, stability and avidity.

cell biology↗

bioRxiv2024

Distribution of calbindin-positive neurons across areas and layers of the marmoset cerebral cortex

The calcium-binding protein calbindin is selectively expressed in specific neuronal populations of the cerebral cortex, including major classes of inhibitory interneurons. We have charted the distribution of calbindin-positive (CB+) neurons across areas and layers of the entire marmoset cortex using a combination of immunohistochemistry, AI-based image segmentation, 3-dimensional reconstruction, and cytoarchitecture-aware registration. CB+ neurons formed 10-20% of the cortical neuronal population, occurring in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+ neurons concentrated in the supragranular layers, there were clear trends in laminar distribution: the relative density in infragranular layers increased with hierarchical level, and the density in layer 4 was lowest in areas involved in sensorimotor integration and action planning. These results reveal new aspects of the cytoarchitectural organization of the primate cortex and demonstrate an efficient approach to mapping the full distribution of neurochemically distinct cell types throughout the brain, readily applicable to most mammalian species and parts of the nervous system.

neuroscience↗