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MemBRAIN: neuronal surface biology

Intracellular Trafficking

Neuronal Polarity

Cell-Surface Proteins

Protein-Protein Interactions

Brain Disease & Aging

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Overview

Research interests

Neurons rely on a precisely organized and dynamic cell surface to establish polarity, form neuronal connections and adapt throughout life. The MemBRAIN laboratory investigates how the neuronal surface is organized and how its disruption contributes to ageing and neurological disease.

Our research spans four interconnected areas:

1. Building neuronal polarity: organizing the neuronal surface

Neurons maintain distinct axonal and dendritic identities that are essential for neuronal communication. We investigate how intracellular trafficking, protein sorting and membrane dynamics establish and maintain the polarized distribution of neuronal surface proteins, and how disruption of this organization affects connectivity and synaptic function.

Relevant publications

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 Biology 17(10): e3000466 (2019).

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).

2. Uncovering the function of neuronal cell-surface proteins

Many neuronal cell-surface proteins remain poorly understood. We investigate their localization, trafficking, molecular interactions and function, with a particular focus on identifying binding partners and defining how these interactions regulate neuronal development, connectivity and synaptic communication. Our goal is to uncover new molecular mechanisms of neuronal function and potential pathways relevant to neurological disease.

Relevant publications

Geyskens C, Raux B, Apóstolo N, Boonen E, Vandensteen J, Marques B, Machado JF, Kumru I, Nys J, Creemers E, Vandenbempt J, Wierda K, Annaert W, Savas JN, de Wit J, Elegheert J, Ribeiro LF. Extracellular neuroligin-ICAM5 coupling drives dendritic growth via actin remodeling. iScience, in press (2026).

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 Journal 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).

3. Membrane and synaptic remodeling during ageing

We investigate how ageing remodels neuronal membranes and synapses, focusing on changes in the abundance, localization, trafficking and interactions of cell-surface and synaptic proteins. Our goal is to identify early molecular alterations that precede cognitive decline and understand why some neuronal circuits remain resilient while others become susceptible to age-related dysfunction.

4. Neuronal surface dysfunction in tauopathies and related neurological disorders

We investigate how alterations at the neuronal surface and synapse intersect with intracellular protein homeostasis in tauopathies and related neurological disorders, including anti-IgLON5 disease. Our goal is to understand how these changes drive synaptic dysfunction and neurodegeneration and to identify early mechanisms that could be targeted to preserve neuronal function.

Experimental approaches

We combine primary rodent neuronal cultures, human neuronal models, rodent brain slices, viral approaches, and genetic and disease models in rodents. Our experimental toolkit includes cellular and molecular biology, live-cell imaging, proteomics, electrophysiology, behavioral analyses, biochemical approaches and CRISPR-Cas9 genome editing.

Other relevant publications

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. Proceedings of the National Academy of Sciences of the USA 111(1): E149–E158 (2014).

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. Science Signaling 14(670): eabb1953 (2021).

Funding

Our research is supported by FCT, the European Commission, CZI, CCDR Centro, and Bluepharma.

Past R&D Projects

Unraveling Anti-IgLON5 disease-associatedtauopathy with neuroproteomics.

2024-04-01

Uncovering the molecular machinery responsible for cargo sorting in neuronal polarization.

2021-03-29

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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Neuroscience and Disease

MemBRAIN: neuronal surface biology

Leader

Luís Ribeiro

Overview

Team

Luís Ribeiro

Leader

Researcher

Alejandra Nunez Torres

PhD Student

Beatriz Ribeiro

PhD Student

Jeannette Schmidt

Researcher

Nuno Apóstolo

Researcher

Rita Afonso

Researcher

Former members

João Francisco Machado

Beatriz Marques

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Publications

R&D Projects

Past R&D Projects

Awards

2023

2021

2020