Article

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: 4.52). 01/2011; 287:1-41. DOI: 10.1016/B978-0-12-386043-9.00001-3
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Andreas F Mack, Jul 03, 2015
0 Followers
 · 
279 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Blood Brain Barrier (BBB) is a specialized vascular structure tightly regulating central nervous system (CNS) homeostasis. Endothelial cells are the central component of the BBB and control of their barrier phenotype resides on astrocytes and pericytes. Interactions between these cells and the endothelium promote and maintain many of the physiological and metabolic characteristics that are unique to the BBB. In this review we describe recent findings related to the involvement of astroglial cells, including radial glial cells, in the induction of barrier properties during embryogenesis and adulthood. In addition, we describe changes that occur in astrocytes and endothelial cells during injury and inflammation with a particular emphasis on alterations of the BBB phenotype. GLIA 2013.
    Glia 12/2013; 61(12). DOI:10.1002/glia.22575 · 6.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aquaporin-4 (AQP4) water channels are located at the basolateral membrane domain of many epithelial cells involved in ion transport and secretion. These epithelial cells separate fluid compartments by forming apical tight junctions. In the brain, AQP4 is located on astrocytes in a polarized distribution: At the border to blood vessels or the pial surface, its density is very high. During ontogeny and phylogeny, astroglial cells go through a stage of expressing tight junctions, separating fluid compartments differently than in adult mammals. In adult mammals, this barrier is formed by arachnoid, choroid plexus, and endothelial cells. The ontogenetic and phylogenetic barrier transition from glial to endothelial cells correlates with the regenerative capacity of neuronal structures: Glial cells forming tight junctions, and expressing no or unpolarized AQP4 are found in the fish optic nerve and the olfactory nerve in mammals both known for their regenerative ability. It is hypothesized that highly polarized AQP4 expression and the lack of tight junctions on astrocytes increase ionic homeostasis, thus improving neuronal performance possibly at the expense of restraining neurogenesis and regeneration.
    The Neuroscientist 05/2012; DOI:10.1177/1073858412447981 · 7.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In human glioblastoma, the blood-brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metalloproteinases (MMP) 2, 3 and 9 in human primary glioblastomas (eight primary tumours, six recurrent tumours). Increase of MMP3- and MMP2/9 immunoreactivities went along with loss of agrin and dystroglycan respectively. On the protein level, AQP4 expression was increased in glioblastoma compared to control tissue. This was not accompanied by an increase of OAPs, suggesting that AQP4 can also occur without forming OAPs. The results underline our concept of the loss of glioma cell polarity as one of the factors responsible for the disturbance of the neurovascular unit and as an explanation for the formation of edemas in the glioblastoma.
    Cell and Tissue Research 02/2012; 347(2):429-41. DOI:10.1007/s00441-011-1321-4 · 3.33 Impact Factor