Expression of alpha-dystrobrevin in blood-tissue barriers: sub-cellular localisation and molecular characterisation in normal and dystrophic mice.
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.
Lien
Chun Fu
CF
Molecular Medicine, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, St. Michael's Building, White Swan Road, Portsmouth, UK.
Hazai
Diana
D
Yeung
Davy
D
Tan
Juraini
J
Füchtbauer
Ernst-Martin
EM
Jancsik
Veronika
V
Górecki
Dariusz C
DC
D000818:Animals; D015824:Blood-Air Barrier / Q000378:metabolism / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000648:ultrastructure; D001814:Blood-Testis Barrier / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D005753:Gastric Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D020868:Gene Silencing; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000648:ultrastructure; D012708:Sertoli Cells / Q000378:metabolism* / Q000648:ultrastructure
D049029:Dystrophin-Associated Proteins; D012333:RNA, Messenger; C098885:dystrobrevin