JOSE JORGE RAMIREZ FRANCO | Aix-Marseille Université (original) (raw)

Papers by JOSE JORGE RAMIREZ FRANCO

Leucine-rich Glioma Inactivated 1 (LGI1) is a glycoprotein secreted by neurons, the deletion of w... more Leucine-rich Glioma Inactivated 1 (LGI1) is a glycoprotein secreted by neurons, the deletion of which leads to Autosomal Dominant Lateral Temporal Lobe Epilepsy. Recently, we showed that LGI1 deficiency in a mouse model (KO-Lgi1) decreased Kv1.1 channel density at the axon initial segment (AIS) and at presynaptic terminals, thus enhancing both intrinsic excitability and glutamate release. However, the precise conditions for rescuing normal excitability in KO-Lgi1 neurons have still not been reported. Here we show that the selective expression of LGI1 in KO-Lgi1 neurons with the use of single-cell electroporation reduces intrinsic excitability, and restores both the Kv1.1 mediated D-type current and Kv1.1 immunostaining at the AIS. In addition, we show that the homeostatic shortening of the AIS length observed in KO-Lgi1 neurons is prevented in neurons electroporated with the Lgi1 gene. Furthermore, we reveal a spatial gradient of both intrinsic excitability and Kv1.1 immunostaining ...

Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously qu... more Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify numbers of neuronal subtypes in defined areas, and of fluorescence signals, derived from RNAscope probes or immunohistochemistry, in defined cellular compartments. As proof-of-principle, we utilized DLAP to analyse subtypes of dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour like voluntary movement, and are differentially affected in Parkinson’s and other diseases. DLAP allows the analysis of large cell numbers from different species, and facilitates the identification of small cellular subpopulations, based on differential mRNA- or protein-expression, and anatomical location. Using DLAP, we identified a small subpopulation of dopaminergic midbrain neurons (~5%), mainly located in the very lateral Substantia nigra (SN), that was immunofluorescence-negative for the plasmalemma dopamine transporter (DAT), with ~30% smaller cel...

Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously qu... more Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify numbers of neuronal subtypes in defined areas, and of fluorescence signals, derived from RNAscope probes or immunohistochemistry, in defined cellular compartments. As proof-of-principle, we utilized DLAP to analyse subtypes of dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour like voluntary movement, and are differentially affected in Parkinson’s and other diseases. DLAP allows the analysis of large cell numbers from different species, and facilitates the identification of small cellular subpopulations, based on differential mRNA- or protein-expression, and anatomical location. Using DLAP, we identified a small subpopulation of dopaminergic midbrain neurons (∼5%), mainly located in the very lateral Substantia nigra (SN), that was immunofluorescence-negative for the plasmalemmal dopamine transporter (DAT). These results have i...

Cellular and Molecular Life Sciences

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and sy... more Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca2+ signaling in MDD are poorly understood. Here, we found that corticosterone-treated mice (Cort-mice) showed altered astrocytic Ca2+ dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca2+ signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons. Downregulation of astrocyte Ca2+ signaling in naïve animals mimicked the synaptic deficits found in Cort-mice. Remarkably, boosting astrocyte Ca2+ signaling with Gq-DREADDS restored mood and cognitive deficits in Cort-mice to control levels. This study highlights the important role of astrocyte Ca2+ signaling for homeostatic control ...

Brain

Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalit... more Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localization of these features, and hence gain broader insights into LGI1’s neurobiology, we analysed the detailed localization of LGI1 and the diversity of its protein interactome, in mouse brains using patient-derived recombinant monoclonal LGI1 antibodies. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neuro-oligodendrocytic and astro-microglial protein complexes. Proteomic data support the presence of LGI1–Kv1–MAGUK complexes, but did not ...

Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalit... more Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localisation of these features, and gain broader insights into LGI1 neurobiology, we analysed the detailed localisation of LGI1, and the diversity of its protein interactome, in mouse brains using recombinant monoclonal LGI1-antibodies derived from encephalitis patients. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neurooligodendrocytic and astro-microglial protein complexes. Proteomic data support the hypothesis that destabilization of Kv1 / MAGUK complexes by autoantibodies could promote excitability, but did not reveal LGI1 complexes with postsynaptic glutamate receptors. Our results extend our understanding of regional, cellular and subcellular LGI1 expression profiles and reveal novel LGI1-associated complexes, thus providing insights into the complex biology of LGI1 and its relationship to seizures and memory loss.

PLoS ONE, 2014

Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they med... more Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde shortterm inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1a protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011

The physiological responses of AMPA receptors can be modulated through the differential expressio... more The physiological responses of AMPA receptors can be modulated through the differential expression of their subunits and by modifying their number at the cell surface. Here we have studied the expression of AMPA receptor subunits (GluR1-4) mRNAs in cerebellar granule cells grown in depolarizing (25 mM K +) medium, and we have evaluated the effect of decreasing the [K + ] in the culture medium for 24 h on both GluR1-4 expression (both mRNA and protein) and their presence at the plasma membrane. The expression of the four AMPAR subunits increases as the [K + ] decreases, although the increase in GluR2 and GluR3 was only observed in the cell soma but not in the dendrites. Calcium entry through L-type calcium channel and CaMKIV activation are responsible for the reduction in the expression of AMPA receptor subunits in cells cultured in depolarizing conditions. Indeed, prolonged reduction of extracellular [K + ] or blockage of L-type calcium channels enhanced both the surface insertion of the four AMPAR subunits and the AMPA response measured through intracellular calcium increase. These findings reveal a balanced increase in functional AMPA receptors at the surface of cells that can trigger strong increases in calcium in response to the persistent reduction of calcium entry.

A) scheme showing the cell treatment. Cerebellar granule cells were exposed to HU-210 (5... more A) scheme showing the cell treatment. Cerebellar granule cells were exposed to HU-210 (5 µM, 10 min), and stimulated with KCl (50 mM, 10 sec) followed by perfusion of NH4Cl (50 mM) (step 1) and silent and active synaptic boutons were determined. Then, cells were treated with the Epac activator 8p-Cpt (50 µM, 4 min; red traces), or with HBM (control; black traces) during the inter-step period, and silent and active synaptic boutons were again quantified (step 2). B) Average responses of the whole population of synaptic boutons are shown for each treatment. Diagrams showing the percentages of silent and awakened synaptic boutons observed after the second pulse in control (C) and in 8-pCpt treated cells (D). E) representative fluorescence images of synaptic boutons responding to two stimulations with 50 mM KCl (10 sec) followed by NH4Cl (50 mM) perfusion in control (HBM) and after 8p-CPT (50 µM, 4 min). Arrow heads indicate individual synaptic boutons. Two examples of individual responses in control (upper traces, black) and another two responses in 8p-CPT (lower traces, red) are also shown. Number of synaptic boutons analyzed (total / silent and active synaptic boutons, n, coverslip number). In control: 358/66 and 292, n = 7. In 8pCpt: 552/139 and 413, n = 9. **p<0.05, when compared to the corresponding control value, Student's t-test.</p

Journal of Neurochemistry, 2017

Cannabinoid receptors mediate short-term retrograde inhibition of neurotransmitter release, as we... more Cannabinoid receptors mediate short-term retrograde inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at excitatory synapses. The responses of individual nerve terminals in VGLUT1-pHluorin transfected cerebellar granule cells to cannabinoids have shown that prolonged activation of cannabinoid type 1 receptors (CB1Rs) silences a subpopulation of previously active synaptic boutons. Adopting a combined pharmacological and genetic approach to study the molecular mechanisms of CB1R-induced silencing, we found that adenylyl cyclase inhibition decreases cAMP levels while it increases the number of silent synaptic boutons and occludes the induction of further silencing by the cannabinoid agonist HU-210. Guanine nucleotide exchange proteins directly activated by cAMP (Epac proteins) mediate some of the presynaptic effects of cAMP in the potentiation of synaptic transmission. ESI05, a selective Epac2 inhibitor, and U-73122, the specific inhibitor of phospholipase C (PLC), both augment the number of silent synaptic boutons. Moreover, they abolish the capacity of the Epac activator, 8-(4-chlorophenylthio)-2 0-O-methyladenosine 3 0 ,5 0-cyclic monophosphate monosodium hydrate, to prevent HU-210-induced silencing consistent with PLC signaling lying downstream of Epac2 proteins. Furthermore, Rab3-interacting molecule (RIM)1a KO cells have many more basally silent synaptic boutons (12.9 AE 3.5%) than wild-type cells (1.1 AE 0.5%). HU-210 induced further silencing in these mutant cells, although 8-(4-chlorophenylthio)-2 0-O-methyladenosine 3 0 ,5 0-cyclic monophosphate monosodium hydrate only awoke the HU-210-induced silence and not the basally silent synaptic boutons. This behavior can be rescued by expressing RIM1a in RIM1a KO cells, these cells behaving very much like wild-type cells. These findings support the hypothesis that a cAMP/Epac/PLC signaling pathway targeting the release machinery appears to mediate cannabinoid-induced presynaptic silencing.

ABSTRACTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electri... more ABSTRACTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential and a biphasic post-inhibitory response. Several studies in rodents have underlined the central role played by the transient A-type current (IA) in the control of pacemaking activity and post-inhibitory rebound properties, thereby influencing both DA release and the physiological response of SNc neurons to incoming inhibitory inputs. Kv4.3 potassium channels were considered to be fully responsible for IA in these neurons, their density being tightly related to pacemaking frequency. In spite of this crucial electrophysiological role, we show that Kv4.3-/- transgenic mice exhibit minor alterations in locomotion and motor learning, although no compensation by functionally overlapping ion channels is observed in Kv4.3-/- SNc DA neurons. Using antigen retrieval immunohi...

Botulinum neurotoxin serotype B (BoNT/B) uses two separate protein and polysialoglycolipid-bindin... more Botulinum neurotoxin serotype B (BoNT/B) uses two separate protein and polysialoglycolipid-binding pockets to interact with synaptotagmin 1/2 and gangliosides. However, an integrated model of this therapeutic tool bound to its neuronal receptors in a native membrane topology is still lacking. Using a panel of in silico and experimental approaches, we present here a new model for BoNT/B binding to neuronal membranes, in which the toxin binds to a preassembled synaptotagmin-ganglioside GT1b complex and a free ganglioside. This interaction allows a lipid-binding loop of BoNT/B to engage in a series of concomitant interactions with the glycone part of GT1b and the transmembrane domain of synaptotagmin. Furthermore, our data provide molecular support for the decrease in BoNT/B sensitivity in Felidae that harbor the natural variant synaptotagmin2-N59Q. These results reveal multiple interactions of BoNT/B with gangliosides and support a novel paradigm in which a toxin recognizes a protein/...

Brain

Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic... more Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, and behavioural and electrophysiological assessments in vivo after mAb injections into the rodent hippocampus. In live cell-based assays, LGI1 epitope recognition was examined with patient sera (n = 31), CSFs (n = 11), longitudinal serum samples (n = 15), and using mAbs (n = 14) generated from peripheral B cells of two patients. All sera and 9/11 CSFs bound both the leucine-rich repeat (LRR) and the epitempin repeat (EPTP) domains of LGI1, with stable ratios of LRR:EPTP antibody levels over time. By contrast, the mAbs derived from both patients recognized either the LRR or EPTP domain. mAbs against both domain specificities showed...

Proceedings of the National Academy of Sciences

Botulinum neurotoxin type B (BoNT/B) recognizes nerve terminals by binding to 2 receptor componen... more Botulinum neurotoxin type B (BoNT/B) recognizes nerve terminals by binding to 2 receptor components: a polysialoganglioside, predominantly GT1b, and synaptotagmin 1/2. It is widely thought that BoNT/B initially binds to GT1b then diffuses in the plane of the membrane to interact with synaptotagmin. We have addressed the hypothesis that a GT1b–synaptotagmin cis complex forms the BoNT/B receptor. We identified a consensus glycosphingolipid-binding motif in the extracellular juxtamembrane domain of synaptotagmins 1/2 and confirmed by Langmuir monolayer, surface plasmon resonance, and circular dichroism that GT1b interacts with synaptotagmin peptides containing this sequence, inducing α-helical structure. Molecular modeling and tryptophan fluorescence spectroscopy were consistent with the intertwining of GT1b and synaptotagmin, involving cis interactions between the oligosaccharide and ceramide moieties of GT1b and the juxtamembrane and transmembrane domains of synaptotagmin, respective...

Frontiers in Cellular Neuroscience, 2016

Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for de... more Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.

Synaptic transmission in the mammalian nervous system is mainly based on chemical synapses. These... more Synaptic transmission in the mammalian nervous system is mainly based on chemical synapses. These synapses contain a cluster of small vesicles that are filled up with neurotransmitter molecules, referred to as synaptic vesicles (SVs) (Sudhof, 2012). Upon the arrival of an action potential to the presynaptic compartment, calcium influx through voltage gated calcium channels (VGCC) promotes the fussion of these SVs with the plasma membrane, leading to the release of the neurotransmitter into the synaptic cleft (Sudhof, 2004). Once in the extracellular space neurotransmitter molecules bind to postsynaptic receptors (Attwell y Gibb, 2005), propagating, in this way, the nerve impulse through neuronal networks. The released neurotransmitter can also activate presynaptic receptors which, in turn, modulates neurotransmitter release. Axonal sites of neurotransmitter release, also known as Active Zones (AZs), contain a high density of VGCC sorrounded by a complex network of proteins that inte...

Neuropharmacology, 2015

Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters... more Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell-and synapse-specificity of the functional relationship between astrocytes and neurons in certain brain circuits remains unknown. In the dorsal striatum, which mainly comprises two intermingled subtypes (striatonigral and striatopallidal) of medium spiny neurons (MSNs) and synapses belonging to two neural circuits (the direct and indirect pathways of the basal ganglia), subpopulations of astrocytes selectively responded to specific MSN subtype activity. These subpopulations of astrocytes released glutamate that selectively activated N-methyl-D-aspartate receptors in homotypic, but not heterotypic, MSNs. Likewise, astrocyte subpopulations selectively regulated homotypic synapses through metabotropic glutamate receptor activation. The results I will present in this seminar show that bidirectional astrocyte-neuron signaling selectively occurs between specific subpopulations of astrocytes, neurons, and synapses.

Neurochemistry International, 2012

Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidze... more Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-c (PPARc), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARc. Our results show that daidzein (0.05-5 lM) decreases cell death induced by exposure to oxygen-glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARc antagonist T0070907 (1 lM). In addition, this phytoestrogen activated PPARc in neuronal cultures, as shown by an increase in PPARc transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARc competitive binding assay. Conversely, daidzein increased PPARc nuclear protein levels and decreased cytosolic ones, suggesting nuclear translocation. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARc activity not mediated by direct binding to the receptor ligandbinding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.

Journal of Cell Science, 2012

Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundame... more Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture incr...

Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously qu... more Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify numbers of neuronal subtypes in defined areas, and of fluorescence signals, derived from RNAscope probes or immunohistochemistry, in defined cellular compartments. As proof-of-principle, we utilized DLAP to analyse subtypes of dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour like voluntary movement, and are differentially affected in Parkinson’s and other diseases. DLAP allows the analysis of large cell numbers from different species, and facilitates the identification of small cellular subpopulations, based on differential mRNA- or protein-expression, and anatomical location. Using DLAP, we identified a small subpopulation of dopaminergic midbrain neurons (∼5%), mainly located in the very lateral Substantia nigra (SN), that was immunofluorescence-negative for the plasmalemmal dopamine transporter (DAT). These results have i...

Cellular and Molecular Life Sciences

Brain

Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalit... more Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localisation of these features, and gain broader insights into LGI1 neurobiology, we analysed the detailed localisation of LGI1, and the diversity of its protein interactome, in mouse brains using recombinant monoclonal LGI1-antibodies derived from encephalitis patients. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neurooligodendrocytic and astro-microglial protein complexes. Proteomic data support the hypothesis that destabilization of Kv1 / MAGUK complexes by autoantibodies could promote excitability, but did not reveal LGI1 complexes with postsynaptic glutamate receptors. Our results extend our understanding of regional, cellular and subcellular LGI1 expression profiles and reveal novel LGI1-associated complexes, thus providing insights into the complex biology of LGI1 and its relationship to seizures and memory loss.

PLoS ONE, 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011

Journal of Neurochemistry, 2017

Brain

Proceedings of the National Academy of Sciences

Frontiers in Cellular Neuroscience, 2016

Neuropharmacology, 2015

Neurochemistry International, 2012

Journal of Cell Science, 2012