Larsen, B. | Search bioRxiv

bioRxiv2018

Systematic Characterization of RhoGEF/RhoGAP Regulatory Proteins Reveals Organization Principles of Rho GTPase Signaling

Rho GTPases control cell morphogenesis and thus fundamental processes in all eukaryotes. They are regulated by 145 RhoGEF and RhoGAP multi-domain proteins in humans. How the Rho signaling system is organized to generate localized responses in cells and prevent their spreading is not understood. Here, we systematically characterized the substrate specificities, localization and interactome of the RhoGEFs/RhoGAPs and revealed their critical role in contextualizing and spatially delimiting Rho signaling. They localize to multiple compartments providing positional information, are extensively interconnected to jointly coordinate their signaling networks and are widely autoinhibited to remain sensitive to local activation. RhoGAPs exhibit lower substrate specificity than RhoGEFs and may contribute to preserving Rho activity gradients. Our approach led us to uncover a multi-RhoGEF complex downstream of G-protein-coupled receptors controlling a Cdc42/RhoA crosstalk. The spatial organization of Rho signaling thus differs from other small GTPases and expands the repertoire of mechanisms governing localized signaling activity.

cell biology↗

bioRxiv2017

Modality-Independent Coding Of Concepts In Prefrontal Cortex

Natural environments convey information through multiple sensory modalities, all of which contribute to peoples percepts. Although it has been shown that visual or auditory content of scene categories can be decoded from brain activity, it remains unclear where and how humans integrate different sensory inputs and represent scene information beyond a specific sensory modality domain. To address this question, we investigated how categories of scene images and sounds are represented in several brain regions. A mixed gender group of healthy human subjects participated the present study, where their brain activity was measured with fMRI while viewing images or listening to sounds of different places. We found that both visual and auditory scene categories can be decoded not only from modality-specific areas, but also from several brain regions in the temporal, parietal, and prefrontal cortex. Intriguingly, only in the prefrontal cortex, but not in any other regions, categories of scene images and sounds appear to be represented in similar activation patterns, suggesting that scene representations in the prefrontal cortex are modality-independent. Furthermore, the error patterns of neural decoders indicate that category-specific neural activity patterns in the middle and superior frontal gyri are tightly linked to categorization behavior. Our findings demonstrate that complex scene information is represented at an abstract level in the prefrontal cortex, regardless of the sensory modality of the stimulus.\n\nStatement of SignificanceOur experience in daily life requires the integration of multiple sensory inputs such as images, sounds, or scents from the environment. Here, for the first time, we investigated where and how in the brain information about the natural environment from multiple senses is merged to form modality-independent representations of scene categories. We show direct decoding of scene categories across sensory modalities from patterns of neural activity in the prefrontal cortex. We also conclusively tie these neural representations to human categorization behavior based on the errors from the neural decoder and behavior. Our findings suggest that the prefrontal cortex is a central hub for integrating sensory information and computing modality-independent representations of scene categories.

neuroscience↗