The stoichiometry of scaffold complexes in living neurons -DLC2 functions as a dimerization engine for GKAP - Université de Montpellier
Article Dans Une Revue Journal of Cell Science Année : 2014

The stoichiometry of scaffold complexes in living neurons -DLC2 functions as a dimerization engine for GKAP

Résumé

Quantitative spatio-temporal characterization of protein interactions in living cells remains a major challenge facing modern biology. We have investigated in living neurons the spatial dependence of the stoichiometry of interactions between two core proteins of the N-methyl-D-aspartate (NMDA)-receptor-associated scaffolding complex, GKAP (also known as DLGAP1) and DLC2 (also known as DYNLL2), using a novel variation of fluorescence fluctuation microscopy called two-photon scanning number and brightness (sN&B). We found that dimerization of DLC2 was required for its interaction with GKAP, which, in turn, potentiated GKAP selfassociation. In the dendritic shaft, the DLC2-GKAP heterooligomeric complexes were composed mainly of two DLC2 and two GKAP monomers, whereas, in spines, the hetero-complexes were much larger, with an average of ,16 DLC2 and ,13 GKAP monomers. Disruption of the GKAP-DLC2 interaction strongly destabilized the oligomers, decreasing the spine-preferential localization of GKAP and inhibiting NMDA receptor activity. Hence, DLC2 serves a hub function in the control of glutamatergic transmission by ordering GKAP-containing complexes in dendritic spines. Beyond illuminating the role of DLC2-GKAP interactions in glutamatergic signaling, these data underscore the power of the sN&B approach for quantitative spatio-temporal imaging of other important protein complexes.
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Dates et versions

hal-03696203 , version 1 (15-06-2022)

Identifiants

  • HAL Id : hal-03696203 , version 1

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Enora Moutin, Vincent Compan, F. Raynaud, Caroline Clerte, Nathalie Bouquier, et al.. The stoichiometry of scaffold complexes in living neurons -DLC2 functions as a dimerization engine for GKAP. Journal of Cell Science, 2014. ⟨hal-03696203⟩
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