Expression of α-dystrobrevin in blood-tissue barriers: sub-cellular localisation and molecular characterisation in normal and dystrophic mice

Abstract

The alpha- and beta-dystrobrevins (DBs) belong to a family of dystrophin-related and dystrophin-associated proteins that are members of the dystrophin-associated protein complex (DAPC). This complex provides a link between the cytoskeleton and the extracellular matrix or other cells. However, specific functions of the two dystrobrevins remain largely unknown, with alpha-DB being believed to have a role mainly in skeletal muscle. Here, we describe previously unknown expression patterns and the localisation and molecular characteristics of alpha-DB isoforms in non-muscle mouse tissues. We demonstrate a highly specific sub-cellular distribution of alpha-DB in organs forming blood-tissue barriers. We show alpha-DB expression and localisation in testicular Sertoli cells, stomach and respiratory epithelia and provide electron-microscopic evidence for its immunolocalisation in these cells and in the central nervous system. Moreover, we present the molecular characterisation of alpha-DB transcript in these tissues and provide evidence for a distinct heterogeneity of associations between alpha-DB and dystrophins and utrophin in normal and dystrophic non-muscle tissues. Together, our results indicate that alpha-DB, in addition to its role in skeletal muscle, may also be required for the proper function of specific non-muscle tissues and that disruption of DAPC might lead to tissue-blood barrier abnormalities.

Glial influence on the blood brain barrier

“…α-Dystrobrevin is another cytoplasmic protein expressed by glial endfeet and known to be present in cells forming blood-tissue barriers (Lien et al, 2007). Dystrobrevins establish complex interactions with dystrophins, syntrophins and other proteins to provide anchorage and support to a multiple set of cytoskeleton components, receptors and channels located in the apical side of the cell membrane (Rees et al, 2007).…”

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

“…Other proteins localized at astrocytic endfeet are those of a multi-subunit complex called dystrophin-associated glycoprotein complex (DGC) [ 12 , 20 ]. The DGC is expressed in various tissues and has been characterized best in skeletal muscle where it connects the cytoskeleton of muscle fibers to the extracellular matrix [ 14 ].…”

α-Dystrobrevin distribution and association with other proteins in human promyelocytic NB4 cells treated for granulocytic differentiation

“…Such multiple -DB isoforms are known to localize differently in cardiac and skeletal muscles [20] and have potentially different physiological roles through their interactions with different proteins within and outside of the DAPC [23]. We have shown that -DB isoforms are expressed in NB4 cells, and that the level of -DB isoforms expression differs in various cell fractions, such as cytosol, nucleus and the hydrophobic cell compartments.…”