Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging.

N. Hoze, D. Nair, E. Hosy, C. Sieben, S. Manley, A. Herrmann, J.-B. Sibarita, D. Choquet, D. Holcman
Proceedings of the National Academy of Sciences. 2012-10-03; 109(42): 17052-17057
DOI: 10.1073/pnas.1204589109

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1. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17052-7. doi:
10.1073/pnas.1204589109. Epub 2012 Oct 3.

Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by
superresolution analysis of live cell imaging.

Hoze N(1), Nair D, Hosy E, Sieben C, Manley S, Herrmann A, Sibarita JB, Choquet
D, Holcman D.

Author information:
(1)Group of Computational Biology and Applied Mathematics, Institute of Biology,
Ecole Normale Supérieure, 46 Rue d’Ulm, 75005 Paris, France.

Simultaneous tracking of many thousands of individual particles in live cells is
possible now with the advent of high-density superresolution imaging methods. We
present an approach to extract local biophysical properties of cell-particle
interaction from such newly acquired large collection of data. Because classical
methods do not keep the spatial localization of individual trajectories, it is
not possible to access localized biophysical parameters. In contrast, by
combining the high-density superresolution imaging data with the present
analysis, we determine the local properties of protein dynamics. We specifically
focus on AMPA receptor (AMPAR) trafficking and estimate the strength of their
molecular interaction at the subdiffraction level in hippocampal dendrites. These
interactions correspond to attracting potential wells of large size, showing that
the high density of AMPARs is generated by physical interactions with an ensemble
of cooperative membrane surface binding sites, rather than molecular crowding or
aggregation, which is the case for the membrane viral glycoprotein VSVG. We
further show that AMPARs can either be pushed in or out of dendritic spines.
Finally, we characterize the recurrent step of influenza trajectories. To
conclude, the present analysis allows the identification of the molecular
organization responsible for the heterogeneities of random trajectories in cells.

DOI: 10.1073/pnas.1204589109
PMCID: PMC3479500
PMID: 23035245 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus