Aquaporin-4 Surface Trafficking Regulates Astrocytic Process Motility and Synaptic Activity in Health and Autoimmune Disease.
Cell Reports. 2019-06-01; 27(13): 3860-3872.e4
DOI: 10.1016/j.celrep.2019.05.097
Lire sur PubMed
Ciappelloni S(1), Bouchet D(2), Dubourdieu N(3), Boué-Grabot E(4), Kellermayer B(2), Manso C(2), Marignier R(5), Oliet SHR(3), Tourdias T(3), Groc L(6).
Author information:
(1)Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, 33077 Bordeaux,
France; Université de Bordeaux, 33077 Bordeaux, France; INSERM U1215, Neurocentre
Magendie, 33077 Bordeaux, France.
(2)Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, 33077 Bordeaux,
France; Université de Bordeaux, 33077 Bordeaux, France.
(3)Université de Bordeaux, 33077 Bordeaux, France; INSERM U1215, Neurocentre
Magendie, 33077 Bordeaux, France.
(4)Université de Bordeaux, 33077 Bordeaux, France; CNRS, Institut des Maladies
Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
(5)INSERM U1028, CNRS UMR 5292, Center for Research in Neuroscience of Lyon,
Lyon, France.
(6)Interdisciplinary Institute for NeuroSciences, CNRS UMR 5297, 33077 Bordeaux,
France; Université de Bordeaux, 33077 Bordeaux, France. Electronic address:
.
Astrocytes constantly adapt their ramified morphology in order to support brain
cell assemblies. Such plasticity is partly mediated by ion and water fluxes,
which rely on the water channel aquaporin-4 (AQP4). The mechanism by which this
channel locally contributes to process dynamics has remained elusive. Using a
combination of single-molecule and calcium imaging approaches, we here
investigated in hippocampal astrocytes the dynamic distribution of the AQP4
isoforms M1 and M23. Surface AQP4-M1 formed small aggregates that contrast with
the large AQP4-M23 clusters that are enriched near glutamatergic synapses.
Strikingly, stabilizing surface AQP4-M23 tuned the motility of astrocyte
processes and favors glutamate synapse activity. Furthermore, human
autoantibodies directed against AQP4 from neuromyelitis optica (NMO) patients
impaired AQP4-M23 dynamic distribution and, consequently, astrocyte process and
synaptic activity. Collectively, it emerges that the membrane dynamics of AQP4
isoform regulate brain cell assemblies in health and autoimmune brain disease
targeting AQP4.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved