Neurosciences

Molecular physiology of the synapse

Rafael Fernández Chacón
Rafael Fernández Chacón
IBiS
Campus Hospital Universitario Virgen del Rocío
Avda. Manuel Siurot, s/n.
41013 · Sevilla

Laboratory: 108

Rafael Fernández Chacón

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  1. Group members
  2. Research areas
  3. Publications

Group: Molecular physiology of the synapse

Directory
Group members Molecular physiology of the synapse
  • Arroyo Saborido, Alejandro.Laboratory Technician (FP2). Technician.
  • Asensio Gómez, Guadalupe.Lda. en Bioquímica
  • Cabrera Romero, Casandra.Técnico de Laboratorio
  • Fernández Chacón, Rafael.Professor of Physiology
  • García-Junco Clemente, Pablo.Doctor en Biología. Postdoctoral.
  • López Begines, Santiago.Investigador Postdoctoral. CIBERNED. Doctor en Biomedicina
  • Martínez Marquez, Emilio.Investigador Predoctoral
  • Mesa Cruz , Cristina.Investigadora Predoctoral
  • Nieto González, José Luis.PhD in Biology. Post-doctoral fellow Juan de la Cierva.
  • Paradela Leal, Carmen.FEA HUVR
  • Reyes León, Santiago.Técnico de Apoyo, Graduado en Biología
  • Rivero Mena, María del Carmen.Laboratory Technician (FP2). Technician.
  • Rubio Pastor, Fátima.Investigadora Predoctoral FPU
  • Sanchez Diaz, Carmen.Investigadora Predoctoral FPU
  • Sánchez Práxedes,, Nieves.Diplomada en Fisioterapia

Research areas

Molecular mechanisms of the functional and structural maintenance of the synapse.

The synapses are the points of contact where neuronal communication takes place that underlies the correct operation of the brain. The nerve endings house synaptic vesicles loaded with neurotransmitters that are released after the arrival of a nerve impulse. This phenomenon can occur thousands of times a day in terminals that are very remote from the neuronal body, as in the case of motor neurones. The nerve endings probably have molecular machinery that allows them to maintain synaptic function independently of the neuronal body. Our laboratory is interested in identifying the components of this machinery and in understanding their mode of operation. A key element is a protein of the synaptic vesicles called Cysteine String Protein-alpha (CSP-alpha). This protein is related to molecular chaperones that participate in the folding and unfolding of proteins. Strangely, genetically modified mice that lack this protein display a neurological phenotype produced by an early degeneration of their nerve endings. Our laboratory uses cultivated neurons from these mice, that form synapses "in vitro" and we study the details of the neuronal communication by means of electro-physiological techniques. In collaboration with the Center of Animal Production and Experimentation of the University of Seville, we have generated transgenic mice that express a green fluorescent protein (synaptopHluorin) that illuminates the nerve endings during synaptic activity. These approaches will be used to understand the functional modifications of the synapse that precede the neurodegeneration of the neurons of the central and peripheral nervous system.

International Journals
Beecroft, SJ; Yau, KS; Allcock, RJN; Mina, K; Gooding, R; Faiz, F; Atkinson, VJ; Wise, C; Sivadorai, P; Trajanoski, D; Kresoje, N; Ong, R; Duff, RM; Cabrera-Serrano, M; Nowak, KJ; Pachter, N; Ravenscroft, G; Lamont, PJ; Davis, MR; Laing, NG
Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
Servian-Morilla, E; Cabrera-Serrano, M; Johnson, K; Pandey, A; Ito, A; Rivas, E; Chamova, T; Muelas, N; Mongini, T; Nafissi, S; Claeys, KG; Grewal, RP; Takeuchi, M; Hao, H; Bonnemann, C; Neto, OLA; Medne, L; Brandsema, J; Topf, A; Taneva, A; Vilchez, JJ; Tournev, I; Haltiwanger, RS; Takeuchi, H; Jafar-Nejad, H; Straub, V; Paradas, C
POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, alpha-dystroglycan hypoglycosylation and a distinctive radiological pattern
ACTA NEUROPATHOLOGICA
Dominguez-Gonzalez, C; Badosa, C; Madruga-Garrido, M; Marti, I; Paradas, C; Ortez, C; Diaz-Manera, J; Berardo, A; Alonso-Perez, J; Trifunov, S; Cuadras, D; Kalko, SG; Blazquez-Bermejo, C; Camara, Y; Marti, R; Mavillard, F; Martin, MA; Montoya, J; Ruiz-Pesini, E; Villarroya, J; Montero, R; Villarroya, F; Artuch, R; Hirano, M; Nascimento, A; Jimenez-Mallebrera, C
Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
SCIENTIFIC REPORTS
Gonzalez-Mera, L; Ravenscroft, G; Cabrera-Serrano, M; Ermolova, N; Dominguez-Gonzalez, C; Arteche-Lopez, A; Soltanzadeh, P; Evesson, F; Navas, C; Mavillard, F; Clayton, J; Rodrigo, P; Servian-Morilla, E; Cooper, ST; Waddell, L; Reardon, K; Corbett, A; Hernandez-Lain, A; Sanchez, A; Perez, JE; Paradas-Lopez, C; Rivas-Infante, E; Spencer, M; Laing, N; Olive, M
HeterozygousCAPN3missense variants causing autosomal-dominant calpainopathy in seven unrelated families
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Cabrera-Serrano, M; Coote, DJ; Azmanov, D; Goullee, H; Andersen, E; McLean, C; Davis, M; Ishimura, R; Stark, Z; Vallat, JM; Komatsu, M; Kornberg, A; Ryan, M; Laing, NG; Ravenscroft, G
A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy
JOURNAL OF MEDICAL GENETICS
Olivé M, Engvall M, Ravenscroft G, Cabrera-Serrano M, Jiao H, Bortolotti CA, Pignataro M, Lambrughi M, Jiang H, Forrest ARR, Benseny-Cases N, Hofbauer S, Obinger C, Battistuzzi G, Bellei M, Borsari M, Di Rocco G, Viola HM, Hool LC, Cladera J, Lagerstedt-Robinson K, Xiang F, Wredenberg A, Miralles F, Baiges JJ, Malfatti E, Romero NB, Streichenberger N, Vial C, Claeys KG, Straathof CSM, Goris A, Freyer C, Lammens M, Bassez G, Kere J, Clemente P, Sejersen T, Udd B, Vidal N, Ferrer I, Edström L, Wedell A, Laing NG
Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions.
Nat Commun.
Nieto-González JL, Gómez-Sánchez L, Mavillard F, Linares-Clemente P, Rivero MC, Valenzuela-Villatoro M, Muñoz-Bravo JL, Pardal R, Fernández-Chacón R
Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α.
Proc Natl Acad Sci U S A.
Domínguez-González C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodríguez FJ, Donati MA, Kleinsteuber K, Martí I, Martín-Hernández E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Álvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Martí R, Paradas C, Hirano M
Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy.
Ann Neurol.
Moore U, Jacobs M, James MK, Mayhew AG, Fernandez-Torron R, Feng J, Cnaan A, Eagle M, Bettinson K, Rufibach LE, Lofra RM, Blamire AM, Carlier PG, Mittal P, Lowes LP, Alfano L, Rose K, Duong T, Berry KM, Montiel-Morillo E, Pedrosa-Hernández I, Holsten S, Sanjak M, Ashida A, Sakamoto C, Tateishi T, Yajima H, Canal A, Ollivier G, Decostre V, Mendez JB, Sánchez-Aguilera Praxedes N, Thiele S, Siener C, Shierbecker J, Florence JM, Vandevelde B, DeWolf B, Hutchence M, Gee R, Prügel J, Maron E, Hilsden H, Lochmüller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Díaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V, Jain COS Consortium
Assessment of disease progression in dysferlinopathy: A 1-year cohort study.
Neurology.
Alonso-Jimenez A, Kroon RHMJM, Alejaldre-Monforte A, Nuñez-Peralta C, Horlings CGC, van Engelen BGM, Olivé M, González L, Verges-Gil E, Paradas C, Márquez C, Garibaldi M, Gallano P, Rodriguez MJ, Gonzalez-Quereda L, Dominguez Gonzalez C, Vissing J, Fornander F, Eisum AV, García-Sobrino T, Pardo J, García-Figueiras R, Muelas N, Vilchez JJ, Kapetanovic S, Tasca G, Monforte M, Ricci E, Gomez MT, Bevilacqua JA, Diaz-Jara J, Zamorano II, Carlier RY, Laforet P, Pelayo-Negro A, Ramos-Fransi A, Martínez A, Marini-Bettolo C, Straub V, Gutiérrez G, Stojkovic T, Martín MA, Morís G, Fernández-Torrón R, Lopez De Munaín A, Cortes-Vicente E, Querol L, Rojas-García R, Illa I, Diaz-Manera J
Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy.
J Neurol Neurosurg Psychiatry.
Garcia-Junco-Clemente P, Tring E, Ringach DL, Trachtenberg JT
State-Dependent Subnetworks of Parvalbumin-Expressing Interneurons in Neocortex.
Cell Rep.
Servián-Morilla E, Cabrera-Serrano M, Rivas-Infante E, Carvajal A, Lamont PJ, Pelayo-Negro AL, Ravenscroft G, Junckerstorff R, Dyke JM, Fletcher S, Adams AM, Mavillard F, Fernández-García MA, Nieto-González JL, Laing NG, Paradas C
Altered myogenesis and premature senescence underlie human TRIM32-related myopathy.
Acta Neuropathol Commun.
Carrasco-Rozas A, Fernández-Simón E, Lleixà MC, Belmonte I, Pedrosa-Hernandez I, Montiel-Morillo E, Nuñez-Peralta C, Llauger Rossello J, Segovia S, De Luna N, Suarez-Calvet X, Illa I, Pompe Spanish Study group, Díaz-Manera J, Gallardo E
Identification of serum microRNAs as potential biomarkers in Pompe disease.
Ann Clin Transl Neurol.
Mavillard F, Madruga-Garrido M, Rivas E, Servián-Morilla E, Ávila-Polo R, Marcos I, Morón FJ, Paradas C, Cabrera-Serrano M
NOVEL intronic CAPN3 Roma mutation alters splicing causing RNA mediated decay.
Ann Clin Transl Neurol.
Fernández-Simón E, Carrasco-Rozas A, Gallardo E, Figueroa-Bonaparte S, Belmonte I, Pedrosa I, Montiel E, Suárez-Calvet X, Alonso-Pérez J, Segovia S, Nuñez-Peralta C, Llauger J, Mayos M, Illa I, Spanish Pompe Study Group, Díaz-Manera J
PDGF-BB serum levels are decreased in adult onset Pompe patients.
Sci Rep.
Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, Fuiza-Luces C, García García J, Morís G, Olivé M, Miralles F, Díaz-Manera J, Caballero C, Méndez-Ferrer B, Martí R, García Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MÁ, Paradas C
Late-onset thymidine kinase 2 deficiency: a review of 18 cases.
Orphanet J Rare Dis.
Fernández-Simón E, Carrasco-Rozas A, Gallardo E, González-Quereda L, Alonso-Pérez J, Belmonte I, Pedrosa-Hernández I, Montiel E, Segovia S, Suárez-Calvet X, Llauger J, Mayos M, Illa I, Barba-Romero MA, Barcena J, Paradas C, Carzorla MR, Creus C, Coll-Cantí J, Díaz M, Domínguez C, Fernández-Torrón R, García-Antelo MJ, Grau JM, López de Munáin A, Martínez-García FA, Morgado Y, Moreno A, Morís G, Muñoz-Blanco MA, Nascimento A, Parajuá-Pozo JL, Querol L, Rojas R, Robledo-Strauss A, Rojas-Marcos Í, Salazar JA, Usón M, Díaz-Manera J
Study of the effect of anti-rhGAA antibodies at low and intermediate titers in late onset Pompe patients treated with ERT.
Mol Genet Metab.
Matteoli M, Menna E, Honer WG, Fernández-Chacón R
Editorial on the Special Issue on SNARE Proteins: A Long Journey of Science in Brain Health and Disease.
Neuroscience
Herrera-Olivares AM, Fernández-Luque JA, Paradas C, Lucia A, Santalla A
Combined HIIT and Resistance Training in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: A Case Report.
Front Physiol.
Morgan J, Butler-Browne G, Muntoni F, Patel K; skeletal muscle stem cells involvement in pathology study group
240th ENMC workshop: The involvement of skeletal muscle stem cells in the pathology of muscular dystrophies 25-27 January 2019, Hoofddorp, The Netherlands.
Neuromuscul Disord.
Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A, Nieto-González JL, Picó S, Hernández IH, Díaz-Hernández JI, Belloc E, Rodolosse A, Parikshak NN, Peñagarikano O, Fernández-Chacón R, Irimia M, Navarro P, Geschwind DH, Méndez R, Lucas JJ.
Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing.
Nature.
Ortega-de San Luis C, Sánchez-García MA, Nieto-González JL, García-Junco-Clemente P, Montero-Sánchez A, Fernández-Chacón R, Pascual A.
Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits
AgingCell
Servián-Morilla E, Robles-Lanuza E, Sánchez-Hidalgo AC, Camacho-García RJ, Páez-Gómez JA, Mavillard F, Saura CA, Martínez-Mir A, Scholl FG.
Proteolytic Processing of Neurexins by Presenilins Sustains Synaptic Vesicle Release
J Neurosci.
. Cabrera-Serrano M, Mavillard F, Biancalana V, Rivas E, Morar B, Hernández-Laín A, Olive M, Muelas N, Khan E, Carvajal A, Quiroga P, Díaz-Manera J, Davis M, Ávila R, Domínguez C, Romero NB, Vílchez JJ, Comas D, Laing NG, Laporte J, Kalaydjieva L, Paradas C.
A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine
Neurology.
Camacho A, Esteban J, Paradas C.
Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.
Neurologia.
Carbonell-Corvillo P, Tristán-Clavijo E, Cabrera-Serrano M, Servián-Morilla E, García-Martín G, Villarreal-Pérez L, Rivas-Infante E, Area-Gómez E, Chamorro-Muñoz MI, Gil-Gálvez A, Miranda-Vizuete A, Martínez-Mir A, Laing N, Paradas C.
A novel MYH7 founder mutation causing Laing distal myopathy in Southern Spain.
NeuromusculDisord.
Coote D, Davis MR, Cabrera M, Needham M, Laing NG, Nowak KJ.
Clinical Utility Gene Card for: Becker muscular dystrophy.
Eur J HumGenet.
Coote DJ, Davis MR, Cabrera M, Needham M, Laing NG, Nowak KJ.
Clinical Utility Gene Card for: autosomal dominant myotoniacongenita (Thomsen Disease).
Eur J HumGenet
Coote DJ, Davis MR, Cabrera M, Needham M, Laing NG, Nowak KJ.
CUGC for Duchenne muscular dystrophy (DMD).
Eur J Hum Genet.
Díaz-Manera J, Fernández-Torrón R, LLauger J, James MK, Mayhew A, Smith FE, Moore UR, Blamire AM, Carlier PG, Rufibach L, Mittal P, Eagle M, Jacobs M, Hodgson T, Wallace D, Ward L, Smith M, Stramare R, Rampado A, Sato N, Tamaru T, Harwick B, Rico Gala S, Turk S, Coppenrath EM, Foster G, Bendahan D, Le Fur Y, Fricke ST, Otero H, Foster SL, Peduto A, Sawyer AM, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V, Jain COS Consortium.
Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.
J NeurolNeurosurgPsychiatry
Garibaldi M, Fattori F, Bortolotti CA, Brochier G, Labasse C, Verardo M, Servián-Morilla E, Gibellini L, Pinti M, Di Rocco G, Raffa S, Pennisi EM, Bertini ES, Paradas C, Romero NB, Antonini G.
Core-rod myopathy due to a novel mutation in BTB/POZ domain of KBTBD13 manifesting as late onset LGMD.
ActaNeuropatholCommun.
Gómez-Andrés D, Díaz-Manera J, Alejaldre A, Pulido-Valdeolivas I, GonzáLez-Mera L, Olivé M, Vilchez JJ, De Munain AL, Paradas C, Muelas N, Sánchez-Montáñez Á, Alonso-Jiménez A, De la Banda MGG, Dabaj I, Bonne G, Munell F, Carlier RY, Quijano-Roy S.
Muscle imaging in laminopathies: Synthesis study identifies meaningful muscles for follow-up
MuscleNerve
Moore UR, Jacobs M, Fernández-Torrón R, Jang J, James MK, Mayhew A, Rufibach L, Mittal P, Eagle M, Cnaan A, Carlier PG, Blamire A, Hilsden H, Lochmüller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Díaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V.
Teenage exercise is associated with earlier symptom onset in dysferlinopathy: a retrospective cohort study.
J NeurolNeurosurg Psychiatry
Taylor RL, Davis M, Turner E, Brull A, Pinos T, Cabrera M, Nowak KJ.
Clinical utility gene card for McArdle disease.
Eur J Hum Genet.
García-Junco-Clemente P, Ikrar T, Tring E, Xu X, Ringach DL, Trachtenberg JT.
An inhibitory pull-push circuit in frontal cortex.
Nat Neurosci
Nieto-González JL, Fernández-Chacón R.
Toward the Inner Nanostructure of a Secretory Vesicle
ACS Nano.
Cabrera-Serrano M, Junckerstorff RC, Alisheri A, Pestronk A, Laing NG, Weihl CC, Lamont PJ.
Cystinosis distal myopathy, novel clinical, pathological and genetic features
Neuromuscul Disord.
Sánchez-Gutiérrez D, Sáez A, Gómez-Gálvez P, Paradas C, Escudero LM.
Rules of tissue packing involving different cell types: human muscle organization.
Sci Rep.
Wu J, Hunt SD, Matthias N, Servián-Morilla E, Lo J, Jafar-Nejad H, Paradas C, Darabi R.
Generation of an induced pluripotent stem cell line (CSCRMi001-A) from a patient with a new type of limb-girdle muscular dystrophy (LGMD) due to a missense mutation in POGLUT1 (Rumi).
Stem Cell Res