NeuroCyto: the neuronal cytoskeleton in health and disease

Team leader: 
Description: 

 

The team started in 2017 as part of the CNRS ATIP program. At NeuroCyto, we are neuronal cell biologists: we want to understand how neurons are organized at the cellular level.

How do neurons differentiate, then build and maintain their complex arborization? How do they establish and conserve their polarity, with the axon and dendrites allowing to send and receive signals? Numerous processes contribute to this organization: elaboration of the cell architecture (thanks to the cytoskeleton), protein transport inside the cell (with diffusion and motor proteins), segregation into distinct compartments (such as axon, synapses, dendritic spines…).

We apply advanced microscopy techniques to directly observe molecular assemblies at the nanoscale in neurons, revealing how they organize the neuron and shape its physiology.

 

Public Summary: 

“NeuroCyto: the neuronal cytoskeleton in physiology and disease” is a team that was created in 2017, as part of  the Neuropathophysiology Institute (INP, CNRS-Aix Marseille University UMR 7051) in beautiful Marseille, France. The team currently has six members, and we welcome trainees all year long. Motivated students are always welcome to contact us! We aim at building a thriving team to make the best possible science by nurturing openness, exchange, and the excitement of discoveries big and small. At NeuroCyto, we want to understand how neurons are organized at the cellular level. How do they differentiate, then build and maintain their complex arborization? How do they establish and conserve their polarity, with the axon and dendrites allowing to send and receive signals? Numerous processes contribute to this organization: elaboration of the cell architecture (thanks to the cytoskeleton), protein transport inside the cell (with diffusion and motor proteins), segregation into distinct compartments (such as an axon, synapses, dendritic spines…). The NeuroCyto team applies advanced microscopy techniques to directly observe molecular assemblies at the nanoscale level in neurons, revealing how they organize the neuron and shape its physiology.

Research topics: 

We are currently focusing on actin organization within axons. Several new axonal actin structures have been discovered by us and others, including submembrane actin rings and intra-axonal actin hotspots and trails. We want to understand the functions of these structures and their relevance for physiological processes such as axonal transport and proper functioning of presynaptic boutons. To do so, we take advantage of the beautiful model of hippocampal neurons in low-density culture, so we can visualize the intricate morphology of individual neurons and follow individual axons. We combine live-cell imaging, targeted manipulations and super-resolution microscopy to connect the dynamic behavior of axonal components to the nanoscale organization of the cytoskeleton, and we devote substantial efforts to implement innovative strategies for the labeling, observation and analysis of these processes. We explore the pathophysiological relevance of our finding by studying cellular models of Alzheimer’s disease, as axonal transport and presynaptic function are compromised in the early stages of the disease.

Role of actin-based nanostructures in axons

Following the identification of new axonal actin structures (rings, hotspots and trails), we want to understand their molecular architecture, assembly mechanism and potential interplay. This is done thanks to a combination of live-cell imaging and super-resolution microscopy techniques as well as innovative strategies to selectively perturb actin within axons. 

Collaboration with the lab of Subhojit Roy, University of Wisconsin, Madison, USA.

New approaches for labeling, imaging and analysis in super-resolution microscopy

To reveal the organization of the axon, an intricate cellular compartment with extensive length and branching, we use optical super-resolution microscopy. We are specialists of Single Molecule Localization Microscopy (SMLM), and we keep working to push the methods, implementing and testing new techniques as soon as they appear. This includes labeling methods for highly-multiplexed acquisition such as DNA-PAINT, automated acquisition strategies, and new image analysis algorithms.

Collaboration with the lab of Ricardo Henriques, UCL/Crick Institute, London, UK and the Abbelight company (Paris, France)

Cell biology of Alzheimer’s disease in relevant cellular models

Impairment of axonal transport and presynaptic release are early-stage events in Alzheimer’s disease. Using our cell biology background, we want to gain a better understanding of why this happens by studying the nanoscale organization of the axon in Alzheimer’s disease models. Starting with classical rodent models, we want to turn to human models thanks to neurons obtained from induced pluripotent stem cells developed by the Nivet team. These models are still poorly characterized at the subcellular organization level, and it will be interesting to look for specific defects in neurons derived from Alzheimer’s disease patients.

Collaboration with the Nivet team at INP.

Partners: 

              

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News

  1. Christophe Leterrier (NeuroCyto team) in Nature Materials

    Christophe Leterrier from the NeuroCyto team just published a study in collaboration with the Cytomorpho lab  - Manuel Théry & Laurent Blanchoin, CEA Paris/Grenoble. Entitled “Self-repair protects microtubules from destruction by molecular motors”, this work demonstrates how motor proteins kinesins and dynein can damage microtubule while walking on them, triggering repair by incorporation of new tubulin monomers inside the microtubule lattice. It was published on Jan.

  2. Christophe Leterrier (NeuroCyto team) in the Journal of Neuroscience: “A Pictorial History of the Neuronal Cytoskeleton”

    Christophe Leterrier, leader of the NeuroCyto team, just published a special review for the 40th anniversary issue of the Journal of Neuroscience. Entitled “A Pictorial History of the Neuronal Cytoskeleton”, it is a journey through the history of the neuronal cytoskeleton in pictures.

  3. The NeuroCyto team receives two ANR grants in 2020

    The NeuroCyto team led by Christophe Leterrier was awarded two collaborative ANR grants in the 2020 call. The first project, “How actin/spectrin scaffold shapes axonal physiology” (ASHA), is coordinated by C. Leterrier in collaboration with the teams of Stéphane Vassilopoulos (Institut de Myologie, Paris) and Emmanuel Nivet at INP.

  4. The Cell Biologist's Guide to Super-Resolution Microscopy

    Christophe Leterrier, leader of the NeuroCyto team, has just published "The Cell Biologist's Guide to Super-Resolution Microscopy", a poster and accompanying review article for the "At A Glance" series of the Journal of Cell Science. He teamed with Guillaume Jacquement and Hellyeh Hamidi from Turku University (Finland), Aexandre Carisey from the Baylor College of Medicine (Houston) and Ricardo Henriques from UCL/Crick Institute (London) to explain the principles and relative strenghts of the various super-resolution techniques hiding in a menagerie of acronyms (SIM, STED, STORM, SMLM...).

  5. Christophe Leterrier on the 46th Nikon Small World Competition Judging Panel

    Christophe Leterrier, NeuroCyto team leader, will be one of the judges for the 46th Nikon Small World photomicrography and Small World in Motion video competitions. He will be the first French researcher to be on the judging panel for this prestigious competition.

  6. L'équipe NeuroCyto dans La Provence
  7. A commentary from Christophe Leterrier in the Journal of Cell Biology

    Christophe Leterrier, leader of the NeuroCyto ATIP team, wrote a Spotlight in the Journal of Cell Biology highlighting a nice recent paper from the group of Pei-Lin Cheng in Taiwan. In this article, Lee et al. showed how degradation of the chloride transporter NKCC1 by proteasomes anchored at the AIS have a key role in lowering the intracellular chloride concentration, leading to the perinatal reversal of GABA effect from excitatory to inhibitory.

  8. New publication of the NeuroCyto team

    First work of 2020 work is out for the NeuroCyto team! A collaboration with Matt Rasband’s lab in Nature Communications. This is a significant paper for the axon initial segment field: Matt’s lab used BioID of key AIS proteins for mapping AIS components. Dozens of new candidates for future studies! We performed super-resolution microscopy of several of the newly identified AIS components. IN particular, we showed that Mical3, a protein linking microtubules and actin, forms clusters along the AIS that are not periodically organized along the actin/spectrin scaffold.

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Open Positions

The Institute of NeuroPhysiopathology (INP) in Marseille is recruiting a research engineer to study subcellular relations between APP and MT5-MMP in Alzheimer's disease

Beginning June 2021; duration 2 years; funded by the Vaincre Alzheimer Foundation

A two-year position as a research engineer is available from June 1, 2021 at the Institute of Neurophysiopathology (INP, University of Aix-Marseille/CNRS) in the team of Dr. Santiago Rivera who studies the physiopathological mechanisms of Alzheimer's disease. The project is developed in collaboration with the NeuroCyto team of Dr Christophe Leterrier also at INP.
The candidate will be involved in a project aimed at elucidating the molecular and subcellular relationships between the MT5-MMP protease and the amyloid precursor protein (APP) in neurons. For this, different approaches will be used, with protein expression by viral vectors in cultured neurons followed by live-cell, super-resolution and HCS microscopy as well as biochemical studies. Experience in one or more of these techniques, especially microscopy, will be appreciated. In addition, experience in molecular biology or data analysis with bioinformatics tools could be useful.
The candidate should have a master's degree or engineering degree in biomedical or biotechnological sciences, be enthusiastic and well-organized, have a taste for detail, a good analytical and learning capacity, be willing to work in a team and have good interpersonal and communication skills.
Applications must be written in French or English and contain: 1) A curriculum vitae. 2) A coverletter. 3) Two letters of reference.
Please send applications no later than March 10 to Dr. Santiago Rivera and Dr. Christophe Leterrier at the following e-mail addresses: santiago.rivera@univ-amu.fr / christophe.leterrier@univ-amu.fr.

Team publications