Neuroscience and Disease

MemBRAIN: neuronal surface biology

Intracellular Trafficking

Neuronal Polarity

Cell-Surface Proteins

Protein-Protein Interactions

Brain Disease & Aging


Research lines

Uncover cellular and molecular mechanisms underlying cell-body – axonal trafficking of neuronal surface cargoes during development.

Elucidate the function of cell surface molecules, such as uncharacterized neuronal cell-adhesion molecules.

Understand the impact of aging on neuronal trafficking underlying the defects in neuronal transmission and cognitive decline.

Characterize pathological mechanisms of aging-associated chronic diseases, such as neurodegenerative disorders.

Overview

Neuronal communication, mediated by synaptic contacts within complex neural networks, is responsible for all our actions and behaviors, including movements, learning, the formation or evocation of memories, and even sleep. For synapses to form and function properly, neurons need to have molecules at the cell surface, such as cell-adhesion molecules. These proteins facilitate the formation of synapses at the appropriate time of development between certain types of neurons, for instance. Thus, the molecular and cellular mechanisms ensuring the transport and presence of these molecules on the neuronal surface are essential for the formation and functioning of the nervous system. When changes occur in these mechanisms that result in alterations in the distribution or function of these proteins, deficiencies in neuronal communication arise, which manifest as neurological changes observed in brain diseases and during aging.

In the MemBRAIN laboratory, we study the molecular and cellular mechanisms that control the distribution of cell-surface proteins in neurons (localization and abundance). Additionally, we also investigate cell-surface proteins with unknown function in the brain. We address these questions during the development of the nervous system, under pathological conditions such as neurodegenerative disorders, and also during aging.

To accomplish this, we use research models such as primary rodent neuronal cultures, human neuronal cultures, rodent brain slices, viral vectors, and genetic and disease models in rodents. Our main techniques include live-cell imaging in neurons, proteomics, electrophysiology, various biochemical assays, as well as cutting-edge approaches in cellular and molecular biology, such as CRISPR-Cas9 for gene editing.

This approach will not only allow us to understand the essential mechanisms underlying the formation and function of the nervous system but also to identify new therapeutic targets and strategies to mitigate the neurological changes that arise in brain diseases and aging.

Featured Articles

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Information about journal articles, updated at 15-12-2024, from platform CIÊNCIAVITAE.

SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function

Luís F. Ribeiro; Ben Verpoort; Julie Nys; Kristel M. Vennekens; Keimpe D. Wierda; Joris de Wit, 2019. PLOS Biology. e3000466 - e3000466. 10. 17. 2019. https://doi.org/10.1371/journal.pbio.3000466 . 10.1371/journal.pbio.3000466 . PLOS Biology

The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors

Savas, Jeffrey N.; Ribeiro, Luís F.; Wierda, Keimpe D.; Wright, Rebecca; DeNardo-Wilke, Laura A.; Rice, Heather C.; Chamma, Ingrid; et al, 2015. Neuron. 764 - 780. 4. 87. 2015. http://dx.doi.org/10.1016/j.neuron.2015.08.007 . 10.1016/j.neuron.2015.08.007 . Neuron

Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation

Ribeiro, Luís F.; Catarino, Tatiana; Carvalho, Mário; Cortes, Luísa; Santos, Sandra D.; Opazo, Patricio O.; Ribeiro, Lyn Rosenbrier; et al, 2021. Science Signaling. 670. 14. 2021. http://dx.doi.org/10.1126/scisignal.abb1953 . 10.1126/scisignal.abb1953 . published Science Signaling

Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus

Ribeiro, L. F.; Catarino, T.; Santos, S. D.; Benoist, M.; van Leeuwen, J. F.; Esteban, J. A.; Carvalho, A. L., 2013. Proceedings of the National Academy of Sciences. E149 - E158. 1. 111. 2013. http://dx.doi.org/10.1073/pnas.1313798111 . 10.1073/pnas.1313798111 . published Proceedings of the National Academy of Sciences

Nuclear import of the DSCAM -cytoplasmic domain drives signaling capable of inhibiting synapse formation

Sachse, Sonja M; Lievens, Sam; Ribeiro, Luís F; Dascenco, Dan; Masschaele, Delphine; Horré, Katrien; Misbaer, Anke; et al, 2019. The EMBO Journal. 6. 38. 2019. http://dx.doi.org/10.15252/embj.201899669 . 10.15252/embj.201899669 . The EMBO Journal


Publications

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Information about journal articles, updated at 15-12-2024, from platform CIÊNCIAVITAE.

Microglial TNFa orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep

Pinto, Maria J; Cottin, Léa; Dingli, Florent; Laigle, Victor; Ribeiro, Luís F; Triller, Antoine; Henderson, Fiona; et al, 2022. The EMBO Journal. 1. 42. 2022. http://dx.doi.org/10.15252/embj.2022111485 . 10.15252/embj.2022111485 . published The EMBO Journal

Heterotypic Amyloid ß interactions facilitate amyloid assembly and modify amyloid structure

Konstantoulea, Katerina; Guerreiro, Patricia; Ramakers, Meine; Louros, Nikolaos; Aubrey, Liam D; Houben, Bert; Michiels, Emiel; et al, 2021. The EMBO Journal. 2. 41. 2021. http://dx.doi.org/10.15252/embj.2021108591 . 10.15252/embj.2021108591 . published The EMBO Journal

Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation

Ribeiro, Luís F.; Catarino, Tatiana; Carvalho, Mário; Cortes, Luísa; Santos, Sandra D.; Opazo, Patricio O.; Ribeiro, Lyn Rosenbrier; et al, 2021. Science Signaling. 670. 14. 2021. http://dx.doi.org/10.1126/scisignal.abb1953 . 10.1126/scisignal.abb1953 . published Science Signaling

Nuclear import of the DSCAM -cytoplasmic domain drives signaling capable of inhibiting synapse formation

Sachse, Sonja M; Lievens, Sam; Ribeiro, Luís F; Dascenco, Dan; Masschaele, Delphine; Horré, Katrien; Misbaer, Anke; et al, 2019. The EMBO Journal. 6. 38. 2019. http://dx.doi.org/10.15252/embj.201899669 . 10.15252/embj.201899669 . The EMBO Journal

SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function

Luís F. Ribeiro; Ben Verpoort; Julie Nys; Kristel M. Vennekens; Keimpe D. Wierda; Joris de Wit, 2019. PLOS Biology. e3000466 - e3000466. 10. 17. 2019. https://doi.org/10.1371/journal.pbio.3000466 . 10.1371/journal.pbio.3000466 . PLOS Biology

Dystrophin deficiency leads to dysfunctional glutamate clearance in iPSC derived astrocytes

Patel, Abdulsamie M.; Wierda, Keimpe; Thorrez, Lieven; van Putten, Maaike; De Smedt, Jonathan; Ribeiro, Luis; Tricot, Tine; et al, 2019. Translational Psychiatry. 1. 9. 2019. http://dx.doi.org/10.1038/s41398-019-0535-1 . 10.1038/s41398-019-0535-1 . published Translational Psychiatry

S-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model

Santos, Ana Isabel; Carreira, Bruno Pereira; Izquierdo-Álvarez, Alicia; Ramos, Elena; Lourenço, Ana Sofia; Filipa Santos, Daniela; Morte, Maria Inês; et al, 2018. Antioxidants & Redox Signaling. 15 - 30. 1. 28. 2018. http://dx.doi.org/10.1089/ars.2016.6858 . 10.1089/ars.2016.6858 . Antioxidants & Redox Signaling

A Modular Organization of LRR Protein-Mediated Synaptic Adhesion Defines Synapse Identity

Schroeder, A.; Vanderlinden, J.; Vints, K.; Ribeiro, L.F.; Vennekens, K.M.; Gounko, N.V.; Wierda, K.D.; de Wit, J., 2018. Neuron. 329 - 344.e7. 2. 99. 2018. http://www.scopus.com/inward/record.url?eid=2-s2.0-85049055996&partnerID=MN8TOARS . 10.1016/j.neuron.2018.06.026 . published Neuron

Trafficking mechanisms of synaptogenic cell adhesion molecules

Ribeiro, L.F.; Verpoort, B.; de Wit, J., 2018. Molecular and Cellular Neuroscience. 34 - 47. 91. 2018. http://www.scopus.com/inward/record.url?eid=2-s2.0-85045454630&partnerID=MN8TOARS . 10.1016/j.mcn.2018.04.003 . published Molecular and Cellular Neuroscience

Neuronal Polarity: MAP2 Shifts Secretory Vesicles into High Gear for Long-Haul Transport down the Axon

Ribeiro, Luís F.; de Wit, Joris, 2017. Neuron. 223 - 225. 2. 94. 2017. http://dx.doi.org/10.1016/j.neuron.2017.04.002 . 10.1016/j.neuron.2017.04.002 . Neuron

The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors

Savas, Jeffrey N.; Ribeiro, Luís F.; Wierda, Keimpe D.; Wright, Rebecca; DeNardo-Wilke, Laura A.; Rice, Heather C.; Chamma, Ingrid; et al, 2015. Neuron. 764 - 780. 4. 87. 2015. http://dx.doi.org/10.1016/j.neuron.2015.08.007 . 10.1016/j.neuron.2015.08.007 . Neuron

GABAA receptor dephosphorylation followed by internalization is coupled to neuronal death in in vitro ischemia

Mele, Miranda; Ribeiro, Luís; Inácio, Ana R.; Wieloch, Tadeusz; Duarte, Carlos B., 2014. Neurobiology of Disease. 220 - 232. 65. 2014. http://dx.doi.org/10.1016/j.nbd.2014.01.019 . 10.1016/j.nbd.2014.01.019 . published Neurobiology of Disease

Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus

Ribeiro, L. F.; Catarino, T.; Santos, S. D.; Benoist, M.; van Leeuwen, J. F.; Esteban, J. A.; Carvalho, A. L., 2013. Proceedings of the National Academy of Sciences. E149 - E158. 1. 111. 2013. http://dx.doi.org/10.1073/pnas.1313798111 . 10.1073/pnas.1313798111 . published Proceedings of the National Academy of Sciences

Regulation of synapse composition by protein acetylation: the role of acetylated cortactin

Catarino, Tatiana; Ribeiro, Luís; Santos, Sandra D.; Carvalho, Ana Luísa, 2012. Journal of Cell Science. 149 - 162. 1. 126. 2012. http://dx.doi.org/10.1242/jcs.110742 . 10.1242/jcs.110742 . published Journal of Cell Science

Contactin-associated Protein 1 (Caspr1) Regulates the Traffic and Synaptic Content of a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)-type Glutamate Receptors

Santos, Sandra D.; Iuliano, Olga; Ribeiro, Luís; Veran, Julien; Ferreira, Joana S.; Rio, Pedro; Mulle, Christophe; Duarte, Carlos B.; Carvalho, Ana Luísa, 2012. Journal of Biological Chemistry. 6868 - 6877. 9. 287. 2012. http://dx.doi.org/10.1074/jbc.m111.322909 . 10.1074/jbc.m111.322909 . published Journal of Biological Chemistry

Activity and Protein Kinase C Regulate Synaptic Accumulation of N-Methyl-d-aspartate (NMDA) Receptors Independently of GluN1 Splice Variant

Ferreira, Joana S.; Rooyakkers, Amanda; She, Kevin; Ribeiro, Luis; Carvalho, Ana Luísa; Craig, Ann Marie, 2011. Journal of Biological Chemistry. 28331 - 28342. 32. 286. 2011. http://dx.doi.org/10.1074/jbc.m111.222539 . 10.1074/jbc.m111.222539 . published Journal of Biological Chemistry

Past R&D Projects

Awards

2023

Collaborative Pair Pilot Project Award (Cycle 2) from Chan Zuckerberg Initiative.

CP2-1-0000000126

2021

Individual Call to Scientific Employment Stimulus - 4th Edition: Assistant Investigator

2021.03397.CEECIND

2020

Marie Skłodowska-Curie Action Individual Fellowship

GA: 101031398

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