The fast diffusion of NKCC1 along the axon is driven by glutamatergic activity - Sorbonne Université Access content directly
Preprints, Working Papers, ... Year : 2022

The fast diffusion of NKCC1 along the axon is driven by glutamatergic activity

Erwan Pol
  • Function : Author
Marion Russeau
Imane Moutkine
Sabine Lévi

Abstract

Summary NKCC1 and KCC2 transporters regulate neuronal chloride homeostasis and thus synaptic inhibition. KCC2 activity is tuned by diffusion-capture in an activity-dependent manner. The mechanisms controlling NKCC1 in neurons are unknown. We found using super-resolution imaging that NKCC1 like KCC2 form nanodomains in the somato-dendritic membrane at extrasynaptic sites and at the periphery of excitatory and inhibitory synapses. NKCC1 nanoclusters are half the size and density in molecules than KCC2 clusters. This is accompanied by a higher mobility of NKCC1 compared to KCC2 in the dendritic membrane, suggesting a weaker NKCC1 anchoring to the cytoskeleton. In contrast, NKCC1, but not KCC2, is confined to endocytic zones, which would explain its controlled surface expression and the fact that endocytic zones would provide a reservoir from which NKCC1 could be released into the membrane. Finally, we show an increased confinement of NKCC1 in axons but not in dendrites upon glutamatergic activity blockade, indicating a selective mechanism of regulation in the axon. We propose that a rapid regulation of NKCC1 by lateral diffusion in the axon would control presynaptic glutamate release and the firing of action potentials.

Domains

Neurobiology

Dates and versions

hal-03974280 , version 1 (05-02-2023)

Identifiers

Cite

Etienne Côme, Erwan Pol, Zaha Merlaud, Juliette Gouhier, Marion Russeau, et al.. The fast diffusion of NKCC1 along the axon is driven by glutamatergic activity. 2023. ⟨hal-03974280⟩
25 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More