Biology subjects

Rennie, M.

Publications and source records attributed to Rennie, M..

4 recordsLinked to original sources

bioRxiv2025

Functional classification of GNAI1 disorder variants in C. elegans uncovers conserved and cell-specific mechanisms of dysfunction

Heterotrimeric G proteins transduce signals from G protein coupled receptors, which mediate key aspects of neuronal development and function. Mutations in the GNAI1 gene, which encodes Gi1, cause a disorder characterized by developmental delay, intellectual disability, hypotonia, and epilepsy. However, the mechanistic basis for this disorder remains unknown. Here, we show that GNAI1 is required for ciliogenesis in human cells and use C. elegans as a whole-organism model to determine the functional impact of seven GNAI1-disorder patient variants. Using CRISPR-Cas9 editing in combination with robust cellular (cilia morphology) and behavioral (chemotaxis) assays, we find that T48I, K272R, A328P, and V334E orthologous variants impact both cilia assembly and function in AWC neurons, M88V and I321T have no impact on either phenotype, and D175V exerts neuron-specific effects on cilia-dependent sensory behaviors. Finally, we validate in human ciliated cell lines that D173V, K270R, and A326P GNAI1 variants disrupt ciliary localization of the encoded human Gi1 proteins similarly to their corresponding orthologous substitutions in the C. elegans ODR-3 (D175V, K272R, and A328P). Overall, our findings determine the in vivo effects of orthologous GNAI1 variants and contribute to mechanistic understanding of GNAI1 disorder pathogenesis as well as neuron-specific roles of ODR-3 in sensory biology. ARTICLE SUMMARYG subunits of heterotrimeric G proteins transduce signaling from G protein coupled receptors and play important roles in cell communication and complex behaviors. Mutations in the GNAI1 gene, which encodes Gi1 protein, have been recently linked to a neurodevelopmental disorder; however, it remains unknown how GNAI1 patient mutations disrupt neuronal development or function to manifest in disease. We demonstrate that GNAI1 is required for ciliogenesis and use C. elegans as a whole-animal model in combination with human cells to identify cell-specific and conserved mechanisms of G dysfunction.

developmental biology↗

bioRxiv2025

PWO proteins are associated with PRC2 since their emergence in vascular plants

PWWP-Domain Interactor of Polycombs 1 (PWO1), also known as PWWP1, interacts with the catalytic subunits of the Polycomb Repressive Complex 2 (PRC2) and, together with PWO2/3 proteins, plays a critical role in the development of Arabidopsis thaliana (At). PWOs are unique to plants and impact chromatin structure by enabling crosstalk between active and repressive epigenetic marks through mechanisms that are not yet fully understood. We aimed to understand the evolution of PWO proteins and whether their interaction with PRC2 has been conserved through evolution. Our study reveals that PWO proteins are present in vascular plants, but absent in bryophytes and green algae. The ancestral clade of PWO proteins includes the Selaginella moellendorffii (Sm) PWO orthologs SmPWOa and SmPWOb. Transient expression assays showed that both AtPWO1 and SmPWOa form nuclear speckles where they tether At, Sm, but also Physcomitrium patens (Pp) PRC2 catalytic subunits, despite the absence of PWO proteins in Pp. The PWO-PRC2 interactions were confirmed by protein-protein analyses. A newly identified evolutionarily conserved short C-terminal alpha-helix (c-motif) in PWO proteins contributes to an interaction interface for PWO-PRC2 binding. SmPWOs partially rescue the pwo1;pwo2 mutant phenotype in Arabidopsis, highlighting the functional conservation of PWOs in vascular plants.

plant biology↗

bioRxiv2023

Repeated Activation of Gαq by neurotransmitters causes age-dependent accumulation of stress granules in C.elegans

Gq proteins mediate signals from neurotransmitters to transduce calcium signals. In PC12 cells, we have shown that Gq stimulation results in retraction of neurites and induces the formation of stress granules that sequester two specific mRNAs, Chbgb and ATP5f1b. Here, we show that repeated activation of Gq in C. elegans adversely reduces lifespan potentially through accumulation of stress granules and inefficient recovery from neurite retraction. In the absence of stimulation, we could not detect significant changes in number of stress granules from Day 1-15 worms. Single Gq activation increases stress granule size through the enlargement of pre-formed particles with younger worms (Day 1-4) being more responsive than older (Day 8). Repeated Gq stimulation impacts the number of particles through the assembly of nascent particles. Additionally, we a systematic rise in the number of AGL-1 stress granules with repeated Gq stimulation suggesting that stress granules accumulate in neurons and sequester mRNAs. This idea is supported by immunofluorescence studies of ATP5f1b as well as changes in peristaltic speed. In addition to stress granule accumulation, we find that repeated Gq activation results in age-dependent morphological defects in mechanosensory neurons. Taken together, studies show that repeated Gq activation negatively influences the health of C.elegans.

neuroscience↗

bioRxiv2019

Winter in water: Differential responses and the maintenance of biodiversity

The ecological consequences of winter in freshwater systems are an understudied but rapidly emerging research area. Here, we argue that winter periods of reduced temperature and light (and potentially oxygen and resources) could play an underappreciated role in mediating the coexistence of species. This may be especially true for temperate and subarctic lakes, where seasonal changes in the thermal environment might fundamentally structure species interactions. With climate change already shortening ice-covered periods on temperate and polar lakes, consideration of how winter conditions shape biotic interactions is urgently needed. Using freshwater fishes in northern temperate lakes as a case study, we demonstrate how physiological trait differences (e.g., thermal preference, light sensitivity) drive differential behavioral responses to winter among competing species. Specifically, some species have a higher capacity for winter activity than others. Existing and new theory is presented to argue that such differential responses to winter can promote species coexistence. Importantly, if winter is a driver of niche differences that weaken competition between relative to within species, then shrinking winter periods could threaten coexistence by tipping the scales in favor of certain sets of species over others.

ecology↗