BBB seminar: Torgeir Holen

Torgeir Holen
Institute of Basic Medical Sciences (IMB) & Centre for Molecular Biology and Neuroscience (CMBN), The National Hospital & University of Oslo

The blood vessels in the brain are surrounded by dense, regular structures called square arrays. Square arrays have been studied by freeze-fracture electron microscopy since 1968 1968 (Kreutziger, 1968; Rash et al., 1974), but their function remains unknown.

Since square arrays disappear in Aquaporin-4 knockout-mice (AQP4 KO) (Verbavatz et al., 1997), and transfection of AQP4 isoforms into cell lines results in a reconstitution of structures similar to square arrays (Furman et al., 2003), the water channel AQP4 is a critical component of square arrays. Aquaporin water channels are well understood with respect to blood plasma filtration and water re-uptake in the kidneys, but their massive presence in the brain is a puzzle.

Whereas square arrays have been studied exclusively by freeze fracture EM for 40 years, we have recently developed biochemical methods to analyze their structure (Sorbo et al., 2007; Sorbo et al., in press). Using this methodology, combined with the discovery of 4 new isoforms of AQP4 (Moe et al., in press), and RNA interference (RNAi) in vivo approaches, we are attempting to understand the elusive function of aquaporins and square arrays in mammalian brains.

References:
 Kreutziger, GO; Proc. 26th Meeting of EM Soc. of America (1968)
 Rash, JE, Staehlin, LA, & Ellisman, MH, Journal of Cell Biology (1974)
 Verbavatz, JM, Ma T, Gobin R & Verkman, AS, J Cell Sci. (1997) 110:2855-60
 Furman CS, Gorelick-Feldman DA, Davidson KG, Yasumura T, Neely JD, Agre P & Rash JE, PNAS (2003) 100:13609-14
 Sorbo JG, Moe SE & Holen T, FEBS Lett. (2007) 581:4884-90.
 Sorbo JG, Moe SE, Ottersen OP & Holen T, Biochemistry (2008, in press)
 Moe SE, Sorbo JG, Sogaard R, Zeuthen T, Ottersen OP & Holen T, Genomics (2008, in press)

 Host: Øyvind Halskau <oyvind.halskau@biomed.uib.no>, Department of Biomedicine