Mapping molecular assemblies with fluorescence microscopy and object-based spatial statistics


Thibault Lagache 1,5, Alexandre Grassart2, Stéphane Dallongeville1, Orestis Faklaris3, Nathalie Sauvonnet2,
Alexandre Dufour1, Lydia Danglot 4 & Jean-Christophe Olivo-Marin 1

1 Institut Pasteur, BioImage Analysis Unit. CNRS UMR 3691. 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
2 Institut Pasteur, Molecular Microbial Pathogenesis Unit. INSERM U1202. 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
3 CNRS UMR7592, Institut Jacques Monod, Université Paris Diderot, 15 rue Hélène Brion, 75013 Paris, France.
4 Inserm U894 Center for Psychiatry and Neuroscience, Team Membrane traffic in healthy and diseased
brain, 102-108 rue de la Santé, 75014 Paris, France.
5 Present address: Department of Biological Sciences, Columbia University, New York NY USA.


Elucidating protein functions and molecular organisation requires to localise precisely single or aggregated molecules and analyse their spatial distributions. We develop a statistical method SODA (Statistical Object Distance Analysis) that uses either micro- or nanoscopy to significantly improve on standard co-localisation techniques. Our method considers cellular geometry and densities of molecules to provide statistical maps of isolated and associated (coupled) molecules. We use SODA with three-colour structured-illumination microscopy (SIM) images of hippocampal neurons, and statistically characterise spatial organisation of thousands of synapses. We show that presynaptic synapsin is arranged in asymmetric triangle with the 2 postsynaptic markers homer and PSD95, indicating a deeper localisation of homer. We then determine stoichiometry and distance between localisations of two synaptic vesicle proteins with 3D-STORM. These findings give insights into the protein organisation at the synapse, and prove the efficiency of SODA to quantitatively assess the geometry of molecular assemblies.

NATURE COMMUNICATIONS | (2018) 9:698 | DOI: 10.1038/s41467-018-03053-x |

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Autres Publications

 02 mars 2018
Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.
 15 février 2018
Mapping molecular assemblies with fluorescence microscopy and object-based spatial statistics
 14 février 2018
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 12 décembre 2017
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 11 septembre 2017
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 01 juin 2017
Targeting demyelination via α-secretases promoting sAPPα release to enhance remyelination in central nervous system
 19 avril 2017
Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons.
 05 avril 2017
Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice.
 14 mars 2017
Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development.
 07 mars 2017
Does virtual reality have a future for the study of episodic memory in aging?
 22 février 2017
Can a 15-sec FLAIR replace conventional FLAIR sequence in stroke MR protocols?
 22 février 2017
Is Unexplained Early Neurological Deterioration After Intravenous Thrombolysis Associated With Thrombus Extension?
 20 février 2017
Bi-directional interplay between proximal and distal inputs to CA2 pyramidal neurons.
 15 février 2017 16 février 2017
The distinctive role of executive functions in implicit emotion regulation.
 11 février 2017
Heavy cannabis use prior psychosis in schizophrenia: clinical, cognitive and neurological evidences for a new endophenotype?
 31 janvier 2017
Neuropsychological improvement after posterior fossa arachnoid cyst drainage.
 26 janvier 2017
Phenotypic continuum between autism and schizophrenia: Evidence from the Movie for the Assessment of Social Cognition (MASC).