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. 

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.

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

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News

  1. Cytoskeleton wars: actin vs microtubules

    The latest collaboration from the NeuroCyto team was just published in the Journal of Cell Science, and asks a simple question: how do microtubule and actin fight or cooperate with each other? The CytoMorpho lab of Manuel Théry and Laurent Blanchoin in Paris and Grenoble used complex in-vitro reconstitution to show how dense actin networks can stop microtubule growth. This is confirmed by Structured Illumination Microscopy images of cells from our Nikon Center of Excellence, showing microtubule stopped at the cell periphery by the dense actin lamellipodium.

  2. The NeuroCyto team SRRFs the super-resolution wave
  3. Cover article from The NeuroCyto team in the Journal of Cell Biology

    The NeuroCyto team published their latest work in the Journal of Cell Biology (article is available here), where they reveal the presence of distinct actin nanostructures within presynapses. The article is featured in the October issue of the journal, and made it to the cover that shows a nice picture of a neuron endogenously tagged for actin using CRISPR/Cas9. It opens new perspectives to understand the multiple roles that have been proposed for actin at presynapses.

  4. New publication of the NeuroCyto team on multicolor super-resolution microscopy

    The NeuroCyto team published a new article in Cell Reports Methods. This is the work of PhD student Karoline Friedl in collaboration with the Abbelight company: we thoroughly characterized two different modalities of simultaneous multicolor Single Molecule Localization Microscopy using a two-camera module. The article can be found here (open access).

  5. Just out: NeuroCyto team in Science
  6. New article from the NeuroCyto Team in Neuron
  7. 2 INP researchers in La Marseillaise "Provence Terre de Science" 

    Each week-end the local newspaper La Marseillaise puts the spotligh on a scientific topic and on a team of research in a scientific page called "Provence Terre de Science". After the page about Alzheimer disease last year (see here), INP research has been highligthed with the interview of Jean Marc Sabatier (Cytoskeleton and Neurophysiopathology team) for his work on venoms, and then Christophe Letterier (NeuroCyto team) for his work on superresolution imaging of neurons, in La Marseillaise week-end editions of may 22nd-24th and

  8. Two articles from the NeuroCyto team in Nature Communications

    The NeuroCyto team has two new articles just out in Nature Communications! Click for more details >>

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Team publications