Primary structure and high expression of human agrin in basement membranes of adult lung and kidney.
Agrin is a heparan sulfate proteoglycan involved in the development of the neuromuscular junction during embryogenesis. In addition to this well-characterized function, agrin may have additional functions in other tissues and during other stages in development. In this study we present the cDNA sequence of human agrin, and demonstrate a high agrin content in adult basement membranes. The N-terminal domain of human agrin is highly similar to that of chick agrin, suggesting a similar function in laminin binding. The presence of three SGXG sequences supports serine-linked glycosylation of the core protein, two sites being particularly favorable for heparan sulfate attachment. Comparison of levels of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation in adult kidney and lung. In both tissues truncated agrin transcripts were detected, lacking the region that encodes the laminin-binding domain. The high transcription levels in lung and kidney corresponded with the accumulation of agrin in the alveolar and glomerular basement membranes, suggesting a filtration-associated function. These data provide new directions for investigating the role of agrin in its different physiological environments, including the basement membranes of the neuromuscular junction, kidney and lung.
Groffen
A J
AJ
Department of Pediatrics, University of Nijmegen, The Netherlands.
Buskens
C A
CA
van Kuppevelt
T H
TH
Veerkamp
J H
JH
Monnens
L A
LA
van den Heuvel
L P
LP
D000367:Age Factors; D018171:Agrin / Q000737:chemistry*; D001485:Basement Membrane / Q000737:chemistry*; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics
D018171:Agrin; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger