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Publication : Orchestrating aquaporin-4 and connexin-43 expression in brain: Differential roles of α1- and β1-syntrophin.

First Author  Rao SB Year  2021
Journal  Biochim Biophys Acta Biomembr Volume  1863
Issue  8 Pages  183616
PubMed ID  33872576 Mgi Jnum  J:323009
Mgi Id  MGI:6765777 Doi  10.1016/j.bbamem.2021.183616
Citation  Rao SB, et al. (2021) Orchestrating aquaporin-4 and connexin-43 expression in brain: Differential roles of alpha1- and beta1-syntrophin. Biochim Biophys Acta Biomembr 1863(8):183616
abstractText  Aquaporin-4 (AQP4) water channels and gap junction proteins (connexins) are two classes of astrocytic membrane proteins critically involved in brain water and ion homeostasis. AQP4 channels are anchored by alpha1-syntrophin to the perivascular astrocytic endfoot membrane domains where they control water flux at the blood-brain interface while connexins cluster at the lateral aspects of the astrocytic endfeet forming gap junctions that allow water and ions to dissipate through the astrocyte syncytium. Recent studies have pointed to an interdependence between astrocytic AQP4 and astrocytic gap junctions but the underlying mechanism remains to be explored. Here we use a novel transgenic mouse line to unravel whether beta1-syntrophin (coexpressed with alpha1-syntrophin in astrocytic plasma membranes) is implicated in the expression of AQP4 isoforms and formation of gap junctions in brain. Our results show that while the effect of beta1-syntrophin deletion is rather limited, double knockout of alpha1- and beta1-syntrophin causes a downregulation of the novel AQP4 isoform AQP4ex and an increase in the number of astrocytic gap junctions. The present study highlight the importance of syntrophins in orchestrating specialized functional domains of brain astrocytes.
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