Interaction of chromosome-6-encoded dystrophin related protein with the extracellular matrix.
Dystrophin-related protein/utrophin is a large, cytoskeletal protein that shares significant sequence similarity with dystrophin. Dystrophin-related protein is known to be enriched where cell-extracellular matrix contacts are well defined; however, the mechanism of dystrophin-related protein enrichment and its functional role(s) at these sites are yet to be defined. Here, we demonstrate that dystrophin-related protein is concentrated in patches of astrocyte membrane in apposition with the extracellular matrix and that the distribution of dystrophin-related protein is temporally modulated by the extracellular matrix constituent laminin. Furthermore, we demonstrate the existence of a specific biochemical association between dystrophin-related protein and laminin in astrocytes. In these astrocytes, the depletion of dystrophin-related protein by the use of antisense dystrophin-related protein oligonucleotides causes marked reduction in the formation of functional substratum-membrane attachments. Taken together, these data suggest that dystrophin-related protein may function in the generation and maintenance of regional substratum-associated membrane specializations, such as those found at the blood-brain barrier.
Khurana
T S
TS
Howard Hughes Medical Institute, Children's Hospital, Boston, MA, USA.
Kunkel
L M
LM
Frederickson
A D
AD
Carbonetto
S
S
Watkins
S C
SC
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D049411:Utrophin
D003598:Cytoskeletal Proteins; D007797:Laminin; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; C483600:Utrn protein, mouse; D049411:Utrophin