Biology subjects

Villa, S.

Publications and source records attributed to Villa, S..

6 recordsLinked to original sources

bioRxiv2026

Site-specific combinatorial ubiquitination drives the targeted degradation of plasma membrane proteins

Cullin-RING E3 ligases (CRLs) ubiquitinate their substrates by recruiting them to complexes containing ubiquitin-conjugating enzymes (UCEs). Ubiquitination proceeds through the transfer of ubiquitin from UCEs to substrate lysines, but the specificity of lysine ubiquitination has not been widely investigated in cells. In this study, we use global ubiquitination profiling to identify sites in the kinase domains of receptor tyrosine kinases (RTKs), EGFR and Her2, that undergo CRL-mediated ubiquitination in cells treated with heterobifunctional degrader molecules. We find that VHL- and Cereblon-dependent degraders trigger the ubiquitination of a common subset of accessible lysines. Using mutagenesis, we show that the number of available ubiquitination sites specifies the extent of RTK degradation. Furthermore, introduction of non-native sites mostly fails to rescue clearance of lysine-deficient RTK mutants. These results highlight the specificity with which UCEs ubiquitinate their substrates and suggest that the ubiquitination of multiple sites governs the efficacy of degraders targeting plasma membrane proteins.

cell biology↗

bioRxiv2026

Rapid expansion and renormalization of parietal gray matter volume following associative learning

The human brain exhibits rapid structural plasticity following learning, yet its temporal dynamics and behavioral relevance remain elusive, particularly for declarative forms of learning. In this study, we tested whether T1-weighted MRI captures rapid structural reorganization following associative memory formation and whether such changes follow an expansion-renormalization trajectory. We combined three independent datasets (N = 198) to quantify gray matter volume (GMV) changes following an associative memory task using voxel-based morphometry across baseline, 2 h, and 12 h post-learning. We observed transient GMV increases in parietal, lateral occipital, and cerebellar regions at 2 h post-learning, which were no longer detectable relative to baseline by 12 h, consistent with rapid renormalization. Critically, GMV changes in left parietal cortex were associated with memory retention, such that greater maintenance of GMV was associated with better retention. In a separate, spatially distinct effect, sleep facilitated renormalization of GMV in the right parietal cortex, an effect that showed no association with memory retention. Our findings provide evidence that human gray matter undergoes hour-scale changes, reflecting dissociable memory- and sleep-related components.

neuroscience↗

bioRxiv2024

Genomics of experimental adaptive radiation in the cryptic coloration of feather lice

1A major challenge faced by living organisms is adaptation to novel environments. This process is poorly understood because monitoring genetic changes in natural populations is difficult. One way to simplify the task is to focus on organisms that can be studied in captivity under conditions that remain largely natural. Feather lice (Insecta, Phthiraptera, Ischnocera) are host-specific parasites of birds that live, feed, and breed solely on feathers. Birds defend themselves against lice, which damage feathers, by killing them with their beaks during bouts of preening. In response, feather lice have evolved background-matching cryptic coloration to help them avoid preening. We experimentally manipulated the color backgrounds of host-specific pigeon lice (Columbicola columbae) by confining them to different colored breeds of rock pigeon (Columba livia) over a period of four years (ca. 60 louse generations). Over the course of the experiment, we sampled lice from pigeons every six months for genomic resequencing, and then calculated allele frequency differences and trajectories to identify putative genomic sites under selection. We documented many loci that changed in response to selection for color. Most loci putatively under selection were unshared among replicate populations of lice, indicating that independent adaptation of distinct lineages to the same novel environment resulted in similar phenotypes driven by different genotypes.

evolutionary biology↗

bioRxiv2023

A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia

Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound healing and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordinates its migration activity and directed motion through the oriented extension of lamellipodia cell protrusions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells remains unknown. Here, we identify a novel MYO6-DOCK7 axis that is critical for spatially restriction of RAC1 activity in a planar polarized fashion in model tissue monolayers. The MYO6-DOCK7 axis specifically controls the extension of cryptic lamellipodia required to drive tissue fluidification and cooperative mode motion in otherwise solid and static carcinoma cell collectives. HighlightsO_LICollective motion of jammed epithelia requires myosin VI activity C_LIO_LIThe MYO6-DOCK7 axis is critical to restrict the activity of RAC1 in a planar polarized fashion C_LIO_LIMYO6-DOCK7-RAC1 activation ensures long-range coordination of movements by promoting orientation and persistence of cryptic lamellipodia C_LIO_LIMyosin VI overexpression is exploited by infiltrating breast cancer cells C_LI

cell biology↗

bioRxiv2019

What if I had a third arm? An EEG study of a supernumerary BCI system

Motor imagery Brain-Computer Interface (MI-BCI) enables bodyless communication by means of the imagination of body movements. Since its apparition, MI-BCI has been widely used in applications such as guiding a robotic prosthesis, or the navigation in games and virtual reality (VR) environments. Although psychological experiments, such as the Rubber Hand Illusion - RHI, suggest the human ability for creating body transfer illusions, MI-BCI only uses the imagination of real body parts as neurofeedback training and control commands. The present work studies and explores the inclusion of an imaginary third arm as a part of the control commands for MI-BCI systems. It also compares the effectiveness of using the conventional arrows and fixation cross as training step (Graz condition) against realistic human hands performing the corresponding tasks from a first-person perspective (Hands condition); both conditions wearing a VR headset. Ten healthy subjects participated in a two-session EEG experiment involving open-close hand tasks, including a third arm that comes out from the chest. The EEG analysis shows a strong power decrease in the sensory-motor areas for the third arm task in both training conditions. Such activity is significantly stronger for Hands than Graz condition, suggesting that the realistic scenario can reduce the abstractness of the third arm and improve the generation of motor imagery signals. The cognitive load is also assessed both by NASA-TLX and Task Load index.

neuroscience↗

bioRxiv2019

A transcriptional toolbox for exploring peripheral neuro-immune interactions.

Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3[1/2] months after the initial injury. This raises the question of whether the commonly used categorisation of pain into \"inflammatory\" and \"neuropathic\" is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq datasets on neurons, macrophages and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data-mining of peripheral neuroimmune interactions.\n\nhttp://rna-seq-browser.herokuapp.com/

neuroscience↗