Functional specialization of retinal Muller cell endfeet depends on an interplay between two syntrophin isoforms.

ABSTRACT: Retinal Müller cells are highly polarized macroglial cells with accumulation of the aquaporin-4 (AQP4) water channel and the inwardly rectifying potassium channel Kir4.1 at specialized endfoot membrane domains abutting microvessels and corpus vitreum. Proper water and potassium homeostasis in retina depends on these membrane specializations. Here we show that targeted deletion of ?1-syntrophin leads to a partial loss of AQP4 from perivascular Müller cell endfeet and that a concomitant deletion of both ?1- and ?1-syntrophin causes a near complete loss of AQP4 from both perivascular and subvitreal endfoot membranes. ?1-syntrophin is normally very weakly expressed in Müller cell endfeet but ?1-syntrophin knockout mice display an increased amount of ?1-syntrophin at these sites. We suggest that upregulation of perivascular ?1-syntrophin restricts the effect of ?1-syntrophin deletion. The present findings indicate that ?1-syntrophin plays an important role in maintaining the functional polarity of Müller cells and that ?1-syntrophin can partially substitute for ?1-syntrophin in AQP4 anchoring. Functional polarization of Müller cells thus depends on an interplay between two syntrophin isoforms.

SUBMITTER: Katoozi S 

PROVIDER: S-EPMC7074989 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature