Biology subjects

Franken, G.

Publications and source records attributed to Franken, G..

3 recordsLinked to original sources

bioRxiv2025

In vivo calcium imaging shows that dorsal root ganglion stimulation predominantly activates large-sized sensory neurons in mice

Dorsal root ganglion (DRG) stimulation is an effective treatment for patients with refractory neuropathic pain. However, the exact mechanisms through which DRG stimulation exerts its analgesic effects, especially in relation to the recruitment of different soma types within the DRG, remains largely unknown. Here, we examined the effect of DRG stimulation (20Hz) on sensory neuron soma recruitment and neuronal responses induced by mechanical hind paw stimulation using in vivo calcium imaging in mice. GCaMP6s was delivered to sensory neurons via an adeno-associated viral vector of serotype 9 (AAV9) injected subcutaneously at P2-5. In adult mice, a stimulation electrode was placed over the L4 DRG, and in vivo calcium imaging was performed. The proportion of responsive neurons and response magnitude was assessed during 30-60 seconds of DRG stimulation at different stimulation amplitudes (33%, 50%, 66%, 80%, 100% of motor threshold (MT)) for small, medium and large-sized subpopulations. In a second experiment, the effect of 30 minutes of DRG stimulation was assessed at 66% MT on neuronal responses induced by mechanical hind paw stimulation during and following DRG stimulation. We show that 20Hz DRG stimulation at clinically relevant parameters mainly activates large-size sensory neurons in mice, both in terms of the proportion of neurons responding as well as response magnitude. There was a small decrease in the proportion of neurons responding to mechanical stimulation during DRG stimulation, which did not recover 30 mins after stimulation had been switched off. By contrast, DRG stimulation did not alter the response magnitude of responding neurons.

neuroscience↗

bioRxiv2023

Galectin-9 regulates dendritic cell contractility and migration via RhoA

Adaptive immunity relies on dendritic cell (DC) migration to transport antigens from tissues to lymph nodes. Galectins, a family of {beta}-galactoside-binding proteins, control cell membrane organisation, exerting crucial roles in multiple physiological processes. Here, we report a novel mechanism underlying cell polarity and uropod retraction. We demonstrate that galectin-9 regulates chemokine-driven and basal DC migration both in humans and mice, indicating a conserved function for this lectin. We identified the underlying mechanism, namely a deficiency in cell rear contractility mediated by galectin-9 interaction with CD44 that in turn regulates RhoA activity. Analysis of DC motility in the 3D tumour-microenvironment revealed galectin-9 is also required for DC infiltration. Moreover, exogenous galectin-9 rescued the motility of tumour-immunocompromised human blood DCs, validating the physiological relevance of galectin-9 in DC migration and underscoring its implications for DC-based immunotherapies. Our results identify galectin-9 as a necessary mechanistic component for DC motility and highlight a novel role for the lectin in regulating cell polarity and contractility.

immunology↗

bioRxiv2020

ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs

Cyclin M (CNNM1-4) proteins maintain cellular and body magnesium (Mg2+) homeostasis. Using various biochemical approaches, we have identified members of the CNNM family as direct interacting partners of ADP-ribosylation factor-like protein 15 (ARL15), a small GTP-binding protein. ARL15 interacts with CNNMs at their carboxyl-terminal conserved cystathionine-{beta}-synthase (CBS) domains. In silico modeling of the interaction using the reported structures of both CNNM2 and ARL15 supports that the small GTPase specifically binds the CBS1 domain. Immunocytochemical experiments demonstrate that CNNM2 and ARL15 co-localize in the kidney, with both proteins showing subcellular localization in the Golgi-apparatus. Most importantly, we found that ARL15 is required for forming complex N-glycosylation of CNNMs. Overexpression of ARL15 promotes complex N-glycosylation of CNNM3. Mg2+ uptake experiments with a stable isotope demonstrate that there is a significant increase of 25Mg2+ uptake upon knockdown of ARL15 in multiple kidney cancer cell lines. Altogether, our results establish ARL15 as a novel negative regulator of Mg2+ transport by promoting the complex N-glycosylation of CNNMs.

biochemistry↗