Molecular scaffolds underpinning macroglial polarization: An analysis of retinal Müller cells and brain astrocytes in mouse

Rune Enger, Georg Andreas Gundersen, Nadia Nabil Haj-Yasein, Martine Eilert-Olsen, Anna Elisabeth Thoren, Gry Fluge Vindedal, Pétur Henry Petersen, Øivind Skare, Maiken Nedergaard, Ole Petter Ottersen, Erlend A. Nagelhus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Key roles of macroglia are inextricably coupled to specialized membrane domains. The perivascular endfoot membrane has drawn particular attention, as this domain contains a unique complement of aquaporin-4 (AQP4) and other channel proteins that distinguishes it from perisynaptic membranes. Recent studies indicate that the polarization of macroglia is lost in a number of diseases, including temporal lobe epilepsy and Alzheimer's disease. A better understanding is required of the molecular underpinning of astroglial polarization, particularly when it comes to the significance of the dystrophin associated protein complex (DAPC). Here, we employ immunofluorescence and immunogold cytochemistry to analyze the molecular scaffolding in perivascular endfeet in macroglia of retina and three regions of brain (cortex, dentate gyrus, and cerebellum), using AQP4 as a marker. Compared with brain astrocytes, Müller cells (a class of retinal macroglia) exhibit lower densities of the scaffold proteins dystrophin and α-syntrophin (a DAPC protein), but higher levels of AQP4. In agreement, depletion of dystrophin or α-syntrophin-while causing a dramatic loss of AQP4 from endfoot membranes of brain astrocytes-had only modest or insignificant effect, respectively, on the AQP4 pool in endfoot membranes of Müller cells. In addition, while polarization of brain macroglia was less affected by dystrophin depletion than by targeted deletion of α-syntrophin, the reverse was true for retinal macroglia. These data indicate that the molecular scaffolding in perivascular endfeet is more complex than previously assumed and that macroglia are heterogeneous with respect to the mechanisms that dictate their polarization.

Original languageEnglish
Pages (from-to)2018-2026
Number of pages9
JournalGLIA
Volume60
Issue number12
DOIs
Publication statusPublished - Dec 2012

Other keywords

  • AQP4
  • Aquaporin
  • Dystrophin
  • Endfeet
  • Glia
  • Mdx3cv
  • Syntrophin

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