Alex Bayés

Alex Bayés
Hospital de la Santa Creu i Sant Pau · Santa Creu i Sant Pau Hospital Research Institute

Ph.D. in Biochemsitry

About

105
Publications
8,809
Reads
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3,107
Citations
Citations since 2016
59 Research Items
2065 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
We are interested in understanding the molecular biology of the synapse and how this relates to higher brain functions such as cognition, memory and learning. We are also interested in how disruptions of normal synaptic molecular physiology results in Mental and Behavioural Disorders, such as Intellectual Disabilities or Autism Spectrum Disorders. Our research takes advantage of Systems Biology approaches to study the synapse as a whole.
Additional affiliations
May 2012 - December 2014
www.molecular-synapse.org
Position
  • Principal Investigator - Molecular Physiology of the Synapse Lab
May 2012 - December 2014
Hospital de la Santa Creu i Sant Pau
Position
  • Principal Investigator - Molecular Physiology of the Synapse Lab
September 2005 - December 2011
Wellcome Sanger Institute
Position
  • PostDoc Position
Education
January 2000 - July 2005
Autonomous University of Barcelona
Field of study
  • Biochemistry and Structural Biology
January 1998 - December 1999
Autonomous University of Barcelona
Field of study
  • Biochemistry
September 1995 - July 1997
Autonomous University of Barcelona
Field of study
  • Biochemistry and Molecular Biology

Publications

Publications (105)
Article
Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...
Article
Full-text available
Loss-of-function variants in SYNGAP1 cause a developmental encephalopathy defined by cognitive impairment, autistic features, and epilepsy. SYNGAP1 splicing leads to expression of distinct functional protein isoforms. Splicing imparts multiple cellular functions of SynGAP proteins through coding of distinct C-terminal motifs. However, it remains un...
Preprint
Full-text available
Loss-of-function variants in SYNAGP1 cause a developmental encephalopathy defined by cognitive impairment, autistic features, and epilepsy. SYNAGP1 splicing leads to expression of distinct functional protein isoforms. Splicing imparts pleiotropic cellular functions of SynGAP proteins through coding of distinct C-terminal motifs. However, it remains...
Article
Full-text available
Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding ε-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD...
Article
In 1981 Jeff Watkins and Dick Evans wrote what was to become a seminal review on excitatory amino acids (EAAs) and their receptors (Watkins and Evans, 1981). Bringing together various lines of evidence dating back over several decades on: the distribution in the nervous system of putative amino acid neurotransmitters; enzymes involved in their prod...
Article
Full-text available
Glutamate is the major excitatory neurotransmitter in vertebrate and invertebrate nervous systems. Proteins involved in glutamatergic neurotransmission, and chiefly glutamate receptors and their auxiliary subunits, play key roles in nervous system function. Thus, understanding their evolution and uncovering their diversity is essential to comprehen...
Article
Full-text available
Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expre...
Preprint
Full-text available
Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type specific vulnerability, their progression and histopathological classification remain controversial. Here using single-cell electrophysiology in vivo and immediate early gene exp...
Article
Full-text available
In mammalian synapses, the function of ionotropic glutamate receptors is critically modulated by auxiliary subunits. Most of these specifically regulate the synaptic localization and electrophysiological properties of AMPA-type glutamate receptors (AMPARs). Here, we comprehensively investigated the animal evolution of the protein families that cont...
Article
Full-text available
Autosomal dominant mutations in GRIN2B are associated with severe encephalopathy, but little is known about the pathophysiological outcomes and any potential therapeutic interventions. Genetic studies have described the association between de novo mutations of genes encoding the subunits of the N-methyl-D-aspartate receptor (NMDAR) and severe neuro...
Article
Full-text available
The SynGAP protein is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. SynGAP has been involved in multiple signaling pathways and can regulate small GTPases with very different functions. Yet, the molecular bases behi...
Preprint
Full-text available
SynGAP-α1 is a splice variant of the neurodevelopmental disorder risk gene, SYNGAP1/Syngap1. α1 encodes the C-terminal PDZ binding motif (PBM) that promotes liquid-liquid phase separation, a candidate process for postsynaptic density organization within excitatory synapses. However, it remains unknown how the endogenous SynGAP PBM regulates synapse...
Preprint
Full-text available
The Syngap1 gene is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural circuit excitability. These cellular and circuit processes are regulated by the ability of Syngap1 gene products to regulate distinct small GTPases. It is known th...
Article
Autosomal dominant mutations in GRIN2B are associated with severe encephalopathy, but little is known about the pathophysiological outcomes and any potential therapeutic interventions. Genetic studies have described the association between de novo mutations of genes encoding the subunits of the N -methyl- d -aspartate receptor (NMDAR) and severe ne...
Article
Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about...
Article
Full-text available
A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify...
Article
Full-text available
Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in met...
Data
Phylogenetic analysis of B. floridae, B. belcheri and B. lanceolatum TLRs. The phylogenetic tree was constructed by maximum-likelihood method (IQ-TREE) using TIR domain sequences of B. floridae, B. belcheri, B. lanceolatum, S. kowalevskii and representative vertebrate TLRs. D. melanogaster Toll sequence was used as an outgroup to root the tree. Seq...
Data
Phylogenetic analysis of BlTLR. The phylogenetic tree was constructed by maximum-likelihood method (IQ-TREE) using full-length protein sequences. BlTLR, BbtTLR1 and representative vertebrate TLR sequences were used in the analysis. D. melanogaster Toll was used as an outgroup to root the tree. Sequences were aligned with MAFFT choosing L-INS-i meth...
Data
TLR sequences of L. variegatus and S. kowalevskii used in the phylogenetic analysis. The TIR domain of each TLR is highlighted in yellow.
Data
Complete phylogenetic analysis of B. lanceolatum TLRs. The phylogenetic tree was constructed by IQ-TREE using full-length protein sequences. This tree is a more detailed version of the tree shown in Figure 1. All the values of SH-aLRT support and ultrafast bootstrap support are shown at the tree nodes. Outgroup, mccTLRs and 6 vertebrate TLR familie...
Data
Protein sequence identity of BlTLR and fish TLR22.
Data
Ectodomain architecture of vertebrate TLRs and BlTLR.
Data
Nucleotide and deduced amino acid sequences of BlTLR. Predicted transcription start site (TSS) is marked with a curved arrow. TATA box is boxed with a rectangle. The putative STAT5 and APIB transcription factor binding sites have a thick underline. The start codon (ATG), the stop codon (TAA) and the polyadenylation signal sequence (AATAAA) are in b...
Data
Predicted domain architecture of BlTLR protein. The domain structure was predicted using the SMART program. Signal peptide (SP), leucine-rich repeat N-terminal domain (LRRNT), leucine-rich repeat (LRR), leucine rich repeat C-terminal domain (LRRCT), Transmembrane domain (TM) and Toll/interleukin-1 receptor (TIR) domain are indicated in figure. Figu...
Data
Vertebrate and invertebrate protein sequences used in the phylogenetic analysis.
Data
Identified DNA and putative protein sequences of TLRs in B. lanceolatum. The TIR domain of each TLR is highlighted in yellow.
Article
Full-text available
Neurotransmitter diseases are a well-defined group of metabolic conditions caused, in most instances, by genes specifically expressed in the presynaptic button. Better understanding of presynaptic molecular physiology, both in normal and pathological conditions, should help develop therapeutical strategies. The clinical relevance of the presynapse...
Article
Cannabis is the most consumed illicit drug worldwide. Its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), affects multiple brain functions, including cognitive performance, by modulating cannabinoid type-1 (CB1) receptors. These receptors are strongly enriched in presynaptic terminals, where they modulate neurotransmitter release....
Article
Background: Synaptic Ras-GTPase-activating protein 1 (SYNGAP1) is an abundant brain-specific protein localized at the postsynaptic density of mammalian excitatory synapses. SYNGAP1 functions as a crucial regulator of downstream intracellular signaling triggered by N-methyl-d-aspartate receptor activation. One of the most important signaling pathwa...
Article
Full-text available
Synapses are centrally involved in many brain disorders, particularly in psychiatric and neurodevelopmental ones. However, our current understanding of the proteomic alterations affecting synaptic performance in the majority of mental illnesses is limited. As a result, novel pharmacotherapies with improved neurological efficacy have been scarce ove...
Chapter
The postsynaptic density (PSD) is a very large protein complex found in excitatory synapses, the most abundant synaptic type in the brain. PSDs contain key proteins to postsynaptic functioning, being closely related to synaptic plasticity and underlying high cognitive abilities such as learning and memory. Biochemical isolation of PSDs has allowed...
Article
Full-text available
Background N-Methyl D-Aspartate receptors (NMDARs) play pivotal roles in synaptic development, plasticity, neural survival, and cognition. Despite recent reports describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatric diseases, little is known about their pathogenic mechanisms and potential therapeutic...
Article
Full-text available
The proteome of human brain synapses is highly complex and is mutated in over 130 diseases. This complexity arose from two whole-genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases; however, its synapse proteome is uncharacterized, and whether the teleost-specific genome duplication (TSGD) influenced...
Data
Functional analysis of Mouse and zebrafish proteinsSheet#1. Cell Location and Protein Type of mouse SYN and PSD proteins as described by the Ingenuity knowledgebase. Proteins found in synaptosomes (SYN) and/or PSDs are indicated.Sheet#2. Cell Location and Protein Type of zebrafish SYN and PSD proteins as described by the Ingenuity knowledgebase. Pr...
Data
Synaptosomal and postsynaptic density proteins identified in mouseSheet#1. List of all proteins identified in mouse synatosomes (SYN) and postsynaptic densities (PSD). For each protein data from each identified peptide is given. Sheet#2. Mass spectrometry quantitative data is provided for mouse proteins. Two label-free quantitative variables are pr...
Data
Synaptosomal and postsynaptic density proteins identified in zebrafishSheet#1. List of all proteins identified in zebrafish synatosomes (SYN) and postsynaptic densities (PSD). For each protein the number and properties of its identified peptides is given.Sheet#2. Mass spectrometry quantitative data is provided for mouse proteins. Two label-free qua...
Data
Supplementary Figures, Supplementary Table, Supplementary Notes and Supplementary References.
Data
Mouse and zebrafish Ensembl protein families Sheet#1. Ensemble gene ID, Ensemble Protein Family ID and Ensemble Family Description are given for all SYN and PSD mouse proteins. The count of proteins for each family is also given. Sheet#2. Ensemble ID, Ensemble Protein Family ID and Ensemble Family Description are given for all SYN and PSD zebrafish...
Data
Mouse and zebrafish domain analysis. List of protein domains found among mouse and zebrafish SYN and PSD components. Also provided are protein domains found in proteins from mouse and zebrafish brain proteomes (M.Brain and Z.Brain) and all protein coding genes (M.Genome or Z.Genome).
Data
Species specific PSD proteins GO analysisSheet#1. Biological Function and Cellular component GO terms enriched among mouse specific PSD proteins.Sheet#2. Biological Function and Cellular component GO terms enriched among zebrafish specific PSD proteins.Sheet#3. Biological Function and Cellular component GO terms enriched among human, mouse and rat...
Data
Proteins from SNARE, ESCRT and HOPS complexes in mammalian PSD. The presence of components of the following protein complexes: SNARE, ESCRT and HOPS, in the postsynaptic density (PSD) of zebrafish, human, mouse and rat, is indicated. For each species a 'YES' 6 denotes that the protein was found and a blank cell denotes that the protein was not iden...
Data
Supporting proteomic sets. Ensembl gene identifiers are given for proteins in the different supporting proteomics sets used in this study.
Data
Mouse and zebrafish SYN/PSD gene orthologsSheet#1. List of SYN and PSD mouse proteins with and ortholog in the zebrafish genome. Orthology type is provided.Sheet#2. List of SYN and PSD zebrafish proteins with and ortholog in the mouse genome. Orthology type is provided.Sheet#3. Mouse SYN and PSD proteins with one or more orthologs in the correspond...
Chapter
The synapse is composed of ∼2000 proteins, and mutations and genetic variants in these proteins result in a large number of disorders, collectively known as synaptopathies. A major subset of synapse proteins assemble with membrane-associated guanylate kinase (MAGUK) proteins into multiprotein complexes known as MAGUK-associated signaling complexes...
Article
The general concept of inborn error of metabolism is currently evolving and travels to the interface between classical biochemistry and cellular biology. Basic neuroscience is providing increasing knowledge about the mechanisms of neurotransmission and novel related disorders are being described. There is a necessity of updating the classic concept...
Article
Full-text available
Background Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human...
Article
Full-text available
Zinc concentrates at excitatory synapses, both at the postsynaptic density and in a subset of glutamatergic boutons. Zinc can modulate synaptic plasticity, memory formation and nociception by regulating transmitter receptors and signal transduction pathways. Also, intracellular zinc accumulation is a hallmark of degenerating neurons in several neur...
Article
Full-text available
Alterations in glutamatergic neurotransmission have long been associated with psychiatric and neurodevelopmental disorders (PNDD), but only recent advances in high-throughput DNA sequencing have allowed interrogation of the prevalence of mutations in glutamate receptors (GluR) among afflicted individuals. In this review we discuss recent work descr...
Article
Full-text available
Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in beha...
Data
Protein Identifications and Proteomic Data. For each identified protein several identification (ID) numbers from biological databases are given. The number of total and uniquely identified peptides for each replicate is also provided. Proteins found with two or more peptides in all replicates are classified as members of the consensus mouse PSD. Hu...
Data
Human and Mouse PSD Proteins Abundance. Individual and average abundance values (iBAQ) for mouse and human PSD proteins are given. Data was normalized and log2 transformed. Normalization was achieved by dividing abundance data points by its species abundance average. Abundance fold difference was defined as the ratio of mouse to human average abund...
Data
PSD Proteins Identified Only in One Species. Proteins only found in human or mouse are shown in separate sheets. For each protein several identification (ID) numbers from biological databases are given. (XLSX)
Data
Protein Classes Overrepresented in Proteins Unique to Each Species. Proteins from the total PSD exclusive to human or mouse were classified independently using the Panther ‘Protein Class’ descriptor. Enrichment analysis was done to determine Protein Classes overrepresented in each species set of exclusive molecules. The Benjamini-Hochberg procedure...