Luís Ribeiro
luisribeiro@uc.pt | ORCID
Activity: 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.
Publications:
Ribeiro LF#, Catarino T, Carvalho M, Cortes L, Santos SD, Opazo PO, Ribeiro LR, Oliveiros B, Choquet D, Esteban JA, Peça J, Carvalho AL#. Ligand-independent activity of the ghrelin receptor modulates AMPA receptors trafficking and supports memory formation. Sci. Signal. 14(670): eabb1953 (2021).
#co-corresponding authors.
Ribeiro LF, Verpoort B, Nys J, Vennekens KM, Wierda KD, de Wit J. SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function. PLoS Biol 17(10): e3000466 (2019).
Sachse SM, Lievens S, Ribeiro LF, Dascenco D, Masschaele D, Horré K, Misbaer A, Vanderroost N, De Smet AS, Salta E, Erfurth ML, Kise Y, Nebel S, Van Delm W, Plaisance S, Tavernier J, De Strooper B, De Wit J, Schmucker D. Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. EMBO J. 38(6): e99669 (2019).
Schroeder A, Vanderlinden J, Vints K, Ribeiro LF, Vennekens KM, Gounko NV, Wierda KD, de Wit J. A modular organization of LRR protein-mediated synaptic adhesion defines synapse identity. Neuron 99(2): 329–344 (2018).
Savas JN, Ribeiro LF, Wierda KD, Wright R, DeNardo-Wilke LA, Rice HC, Chamma I, Wang YZ, Zemla R, Lavallée-Adam M, Vennekens KM, O'Sullivan ML, Antonios JK, Hall EA, Thoumine O, Attie AD, Yates JR 3rd, Ghosh A, de Wit J. The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors. Neuron 87(4): 764–780 (2015).
Ribeiro LF, Catarino T, Santos SD, Benoist M, van Leeuwen JF, Esteban JA, Carvalho AL. Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus. Proc. Natl. Acad. Sci. U.S.A. 111(1): E149–E158 (2014).
