Structure and Functions of Aquaporin-4-Based Orthogonal Arrays of Particles

Institute of Pathology, University of Tübingen, Tübingen, Germany.
International review of cell and molecular biology (Impact Factor: 3.42). 01/2011; 287:1-41. DOI: 10.1016/B978-0-12-386043-9.00001-3
Source: PubMed


Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membrane of diverse cells which were initially discovered by means of the freeze-fracturing technique. This technique, developed in the 1960s, was important for the acceptance of the fluid mosaic model of the biological membrane. OAPs were first described in liver cells, and then in parietal cells of the stomach, and most importantly, in the astrocytes of the brain. Since the discovery of the structure of OAPs and the identification of OAPs as the morphological equivalent of the water channel protein aquaporin-4 (AQP4) in the 1990s, a plethora of morphological work on OAPs in different cells was published. Now, we feel a need to balance new and old data on OAPs and AQP4 to elucidate the interrelationship of both structures and molecules. In this review, the identity of OAPs as AQP4-based structures in a diversity of cells will be described. At the same time, arguments are offered that under pathological or experimental circumstances, AQP4 can also be expressed in a non-OAP form. Thus, we attempt to project classical work on OAPs onto the molecular biology of AQP4. In particular, astrocytes and glioma cells will play the major part in this review, not only due to our own work but also due to the fact that most studies on structure and function of AQP4 were done in the nervous system.

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    • "In freeze-fracture electron microscopy, astroglial membranes can be identified by orthogonal arrays of particles (OAPs) found in high densities on subpial and perivascular endfeet in the adult brain. OAPs have been shown to consist at least in part of AQP4 (Rash et al., 1998; Wolburg et al., 2011). We detected OAPs in low densities earlier than previously reported yet consistent with the immunocytochemical data appearing at different developing times depending on location. "
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    ABSTRACT: The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis and water exchange in the brain. In adult mammalian brains, it is expressed in astrocytes, mainly, and in high densities in the membranes of perivascular and subpial endfeet. Here, we addressed the question how this polarized expression is established during development. We used immunocytochemistry against AQP4, zonula occludens protein-1, glial fibrillary acidic protein, and β -dystroglycan to follow astrocyte development in E15 to P3 NMRI mouse brains, and expression of AQP4. In addition we used freeze-fracture electron microscopy to detect AQP4 in the form of orthogonal array of particles (OAPs) on the ultrastructural level. We analyzed ventral, lateral, and dorsal regions in forebrain sections and found AQP4 immunoreactivity to emerge at E16 ventrally before lateral (E17) and dorsal (E18) areas. AQP4 staining was spread over cell processes including radial glial cells in developing cortical areas and became restricted to astroglial endfeet at P1 to P3. This was confirmed by double labeling with GFAP. In freeze-fracture replicas OAPs were found with a slight time delay but with a similar ventral to dorsal gradient. Thus, AQP4 is expressed in the embryonic mouse brain starting at E16, earlier than previously reported. However a polarized expression necessary for homeostatic function and water balance emerges at later stages around and after birth.
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    • "AQP4 is anchored to the astrocyte cytoarchitecture via a-syntrophin, a component of the dystrophin-dystroglycan complex (Neely et al., 2001) that links dystrophin-associated proteins (DAP) such as dystroglycan, with various cytoskeletal components. DAP, dystroglycan, as well as other molecules preferentially expressed at the astrocyte endfeet are responsible for the polarized expression of AQP4 in CNS astrocytes (Amiry-Moghaddam and Ottersen 2003; Frigeri et al., 2001; Lien et al., 2012) and are associated with a high density of orthogonal arrays of particles (OAPs) that become less frequent in deeper areas of the neuropil (Wolburg et al., 2011). Both AQP4 knockout animals and mice specifically deficient for AQP4 in astrocytes have a significant reduction in brain water uptake and have reduced brain edema following stroke, as compared to WT animals (Haj-Yasein et al., 2011; Manley et al., 2000). "
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    • "In the following airways, the basolateral membrane domains of columnar cells of the trachea and of bronchus surface epithelial cells were also positive for AQP4 (Nielsen and others 1997). Alveolar cells are also believed to express AQP4 at least in some species (Kreda and others 2001; Verkman 2007; Wolburg and others 2011). In the urinary tract, AQP4 is expressed in the basolateral membrane domain of principal cells in the kidney collecting duct, along with AQP2 in the apical membrane of these cells (King and others 2004) (Fig. 2B). "
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