Biology subjects

Reynaud, A.

Publications and source records attributed to Reynaud, A..

8 recordsLinked to original sources

bioRxiv2021

Tumor protein D54 binds intracellular nanovesicles via an amphipathic lipid packing sensor (ALPS) motif

Tumor Protein D54 (TPD54) is an abundant cytosolic protein that belongs to the TPD52 family, a family of four proteins (TPD52, 53, 54 and 55) that are overexpressed in several cancer cells. Even though the functions of these proteins remain elusive, recent investigations indicate that TPD54 binds to very small cytosolic vesicles with a diameter of ca. 30 nm, half the size of classical transport vesicles (e.g. COPI and COPII). Here, we investigated the mechanism of intracellular nanovesicle capture by TPD54. Bioinformatical analysis suggests that TPD54 contains a small coiled-coil followed by several amphipathic helices, which could fold upon binding to lipid membranes. One of these helices has the physicochemical features of an Amphipathic Lipid Packing Sensor (ALPS) motif, which, in other proteins, enables membrane binding in a curvature-dependent manner. Limited proteolysis, CD spectroscopy, tryptophan fluorescence and cysteine mutagenesis coupled to covalent binding of a membrane sensitive probe show that binding of TPD54 to small liposomes is accompanied by large structural changes in the amphipathic helix region. TPD54 binding to artificial liposomes is very sensitive to liposome size and to lipid unsaturation but is poorly dependent on lipid charge. Cellular investigations confirmed the key role of the ALPS motif in vesicle targeting. Surprisingly, the vesicles selected by TPD54 poorly overlap with those captured by the golgin GMAP-210, a long vesicle tether at the Golgi apparatus, which displays a dimeric coiled-coil architecture and an N-terminal ALPS motif. We propose that TPD54 recognizes nanovesicles through a combination of ALPS-dependent and -independent mechanisms.

cell biology↗

bioRxiv2020

NFAT are Essential and Redundant Actors for Leukemia Initiating Potential in T-cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few available targeted therapies. We previously reported that the phosphatase calcineurin (Cn) is required for LIC (leukemia Initiating Capacity) potential of T-ALL pointing to Cn as an interesting therapeutic target. Calcineurin inhibitors have however unwanted side effect. NFAT transcription factors play crucial roles downstream of calcineurin during thymocyte development, T cell differentiation, activation and anergy. Here we elucidate NFAT functional relevance in T-ALL. Using murine T-ALL models in which Nfat genes can be inactivated either singly or in combination, we show that NFATs are required for T-ALL LIC potential and essential to survival, proliferation and migration of T-ALL cells. We also demonstrate that Nfat genes are functionally redundant in T-ALL and identified a node of genes commonly deregulated upon Cn or NFAT inactivation, which may serve as future candidate targets for T-ALL.

cancer biology↗

bioRxiv2020

Ocular Dominance Plasticity: Measurement Reliability and Variability

AO_SCPLOWBSTRACTC_SCPLOWIn the last decade, studies have shown that short-term monocular deprivation strengthens the deprived eyes contribution to binocular vision. However, the magnitude of the change in eye dominance after monocular deprivation (i.e., the patching effect) has been found to be different between for different methods and within the same method. There are three possible explanations for the discrepancy. First, the mechanisms underlying the patching effect that are probed by different measurement tasks might exist at different neural sites. Second, test-retest variability in the measurement might have led to inconsistencies, even within the same method. Third, the patching effect itself in the same subject might fluctuate across separate days or experimental sessions. To explore these possibilities, we assessed the test-retest reliability of the three most commonly used tasks (binocular rivalry, binocular combination, and dichoptic masking) and the repeatability of the shift in eye dominance after short-term monocular deprivation for each of the task. Two variations for binocular phase combination were used, at one and many contrasts of the stimuli. Also, two variations of the dichoptic masking task was tested, in which the orientation of the mask grating was either horizontal or vertical. This makes five different measurement methods in all. We hope to resolve some of the inconsistencies reported in the literature concerning this form of visual plasticity. In this study, we also aim to recommend a measurement method that will allow us to better understand its physiological basis and the underpinning of visual disorders.

neuroscience↗

bioRxiv2020

Monocular vision is intrinsically unstable: a side-effect of binocular homeostasis

It is now accepted that short-term deprivation of one eye in adults results in not only a post-deprivation strengthening of the vision in the previously deprived eye but also a deterioration in the vision of the previously non-patched eye. Such monocular deprivation of 1-2 hours induces changes that last approximately 30-90 minutes. There is some support for this neuroplastic effect being the consequence of a change in the contrast gain within the binocular circuity. What is not known is when these changes in gain are initiated. One possibility is that they are initiated only once the patch is removed. The other possibility is that they are the result of a slow build up from the moment the patch is first applied. In this study, we measure monocular contrast detection thresholds of the non-deprived eye over time during the deprivation of the other eye. We show that contrast threshold increases over time during the deprivation of the other eye. This observation suggest that the patching effect is mediated by a slow build up over the deprivation period: reducing the vision of the non-deprived eye and enhancing the vision of the deprived eye reflecting reciprocal changes in sensitivity. These results highlight a hitherto unknown feature of human vision, namely that monocular vision per se is intrinsically unstable which is a consequence of the reciprocal inhibitory circuits that homeostatically regulate binocular vision. This questions a whole corpus of studies of visual function that rely on the assumption that monocular vision is intrinsically stable.

neuroscience↗

bioRxiv2019

Revealing α oscillatory activity using voltage-sensitive dye imaging in monkey V1

The relevance of oscillations (7-12Hz) in neural processing, although recognized long ago, remains a major research question in the field. While intensively studied in humans, oscillations appear much less often investigated (and observed) in monkeys. Here we wish to provide data from non-human primates on stimulus-related rhythm. Indeed, in humans, EEG is enhanced in response to non-periodic dynamic visual stimulation ("perceptual echoes" or to a static stimulus ("flickering wheel illusion"). Do the same visual patterns induce an oscillatory response in monkey V1? We record voltage-sensitive dye signals from three anesthetized monkeys to investigate the population-based oscillatory neural response that is not resulting from attention-related feedback signals. We revealed oscillations in monkey V1 which, when they occur, react in a manner comparable to human studies.

neuroscience↗

bioRxiv2018

Norepinephrine improves attentional orienting in a predictive context

The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes under the influence of NE and to characterize these influences. We tested the effects of atomoxetine injections (ATX), a NE-reuptake inhibitor that boosts the level of NE in the brain, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more mitigated. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

neuroscience↗

bioRxiv2018

Visual plasticity and exercise revisited: no evidence for a \"cycling lane\"

Experiments using enriched environments have shown that physical exercise modulates visual plasticity in rodents. A recent study (Lunghi & Sale, 2015, doi: 10.1016/j.cub.2015.10.026) investigated whether exercise also affects visual plasticity in adult humans. The plastic effect they measured was the shift in ocular dominance caused by 2 hours of monocular deprivation (e.g. by an eye patch). They used a binocular rivalry task to measure this shift. They found that the magnitude of the shift was increased by exercise during the deprivation period. This effect of exercise was later disputed by a study that used a different behavioural task (Zhou et al., 2017, doi: 10.1155/2017/4780876). Our goal was to determine whether the difference in task was responsible for that studys failure to find an exercise effect. We set out to replicate Lunghi & Sale (2015). We measured ocular dominance with a rivalry task before and after 2 hours of deprivation. We measured data from two conditions in 30 subjects. On two separate days they either performed exercise or rested during the deprivation period. Contrary to the previous study, we find no significant effect of exercise. We hypothesise that exercise may affect rivalry dynamics in a way that interacts with the measurement of the deprivation effect.

neuroscience↗

bioRxiv2018

Suppressive waves disambiguate the representation of long-range apparent motion in awake monkey V1

The \"apparent motion\" illusion is evoked when stationary stimuli are successively flashed in spatially separated positions. It depends on the precise spatial and temporal separations of the stimuli. For large spatiotemporal separation, the long-range apparent motion (lrAM), it remains unclear how the visual system computes unambiguous motion signals. Here we investigated whether intracortical interactions within retinotopic maps could shape a global motion representation at the level of V1 population in response to a lrAM. In fixating monkeys, voltage-sensitive dye imaging revealed the emergence of a spatio-temporal representation of the motion trajectory at the scale of V1 population activity, shaped by systematic backward suppressive waves. We show that these waves are the expected emergent property of a recurrent gain control fed by the horizontal intra-cortical network. Such non-linearities explain away ambiguous correspondence problems of the stimulus along the motion path, preformating V1 population response for an optimal read-out by downstream areas.

neuroscience↗