Biology subjects

Francois, E.

Publications and source records attributed to Francois, E..

3 recordsLinked to original sources

bioRxiv2026

Salmonella exploits USP32 to coordinate Rab14 and Rab11 recycling pathways for intracellular survival

Many intracellular bacterial pathogens establish membrane-bound niches derived from host material to survive and replicate within host cells. These compartments are carved through subversion of host intracellular trafficking pathways to modulate the composition of the vacuolar membrane. Although recycling-associated small Rab GTPases are frequently observed at infection sites, their role in membrane remodeling and cargo sorting has remained poorly understood. Here, we leverage the extensive early membrane remodeling occurring during Salmonella infection to dissect this process. Using endogenously tagged cell lines, we characterize the dynamics of the recycling small GTPases Rab14 and Rab11 at Salmonella intracellular infection sites. We report that Rab14 recruits its effector Rufy1, which mediates sorting of CI-M6PR through recycling tubules. Subsequently, Rab11 disperses the newly formed recycling endosomes by interacting with its effector Fip3 for retrograde transport. This pathway is controlled by the deubiquitinating enzyme USP32, which targets both Rab14 and Rab11, enhancing their interactions with Rufy1 and Fip3, respectively. We further show that USP32 is recruited to the infection site via local enrichment of phosphatidylserine-positive membranes, a process triggered by the Salmonella effector proteins SopE/E2. Importantly, silencing USP32 significantly impairs intracellular bacterial survival. Our findings reveal a remarkable exploitation of host signaling and trafficking pathways by Salmonella to construct a replication-permissive niche. Targeting these pathways may offer new strategies for therapeutic intervention against intracellular bacterial infections.

cell biology↗

bioRxiv2021

A terrain treadmill to study small animal locomotion through large obstacles

A major challenge to understanding locomotion in complex 3-D terrain with large obstacles is to create tools for controlled, systematic lab experiments. Existing terrain arenas only allow observations at small spatiotemporal scales ([~]10 body length, [~]10 stride cycles). Here, we create a terrain treadmill to enable high-resolution observations of animal locomotion through large obstacles over large spatiotemporal scales. An animal moves through modular obstacles on an inner sphere, while a rigidly-attached, concentric, transparent outer sphere rotated with the opposite velocity via closed-loop feedback to keep the animal on top. During sustained locomotion, a discoid cockroach moved through pillar obstacles for 25 minutes ({approx} 2500 strides) over 67 m ({approx} 1500 body lengths), and was contained within a radius of 4 cm (0.9 body length) for 83% of the duration, even at speeds of up to 10 body length/s. The treadmill enabled observation of diverse locomotor behaviors and quantification of animal-obstacle interaction. Summary StatementA device keeps a small animal on top of a sphere while it traverses obstacles, creating a "terrain treadmill" to study locomotion over a long time and distance at high-resolution.

animal behavior and cognition↗

bioRxiv2018

KCC2 regulates neuronal excitability and hippocampal activity via interaction with Task-3 channels

The K+/Cl- co-transporter KCC2 (SLC12A5) regulates neuronal transmembrane chloride gradients and thereby controls GABA signaling in the brain. KCC2 downregulation is observed in several neurological and psychiatric disorders including epilepsy, neuropathic pain and autism spectrum disorders. Paradoxical, excitatory GABA signaling is usually assumed to contribute to abnormal network activity underlying the pathology. We tested this hypothesis and explored the functional impact of chronic KCC2 downregulation in the rat dentate gyrus. Although the reversal potential of GABAA receptor currents was depolarized in KCC2 knockdown neurons, this shift was fully compensated by depolarization of their resting membrane potential. This effect was due to downregulation of Task-3 leak potassium channels that we show require KCC2 for membrane trafficking. Increased neuronal excitability upon KCC2 suppression altered dentate gyrus rhythmogenesis that could be normalized by chemogenetic hyperpolarization. Our data reveal KCC2 downregulation engages complex synaptic and cellular alterations beyond GABA signaling that concur to perturb network activity, thus offering novel targets for therapeutic intervention.

neuroscience↗