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 ot her tissues and during other stages in development. In this study we p resent the cDNA sequence of human agrin, and demonstrate a high agrin content in adult basement membranes. The N-terminal domain of human ag rin is highly similar to that of chick agrin, suggesting a similar fun ction in laminin binding. The presence of three SGXG sequences support s serine-linked glycosylation of the core protein, two sites being par ticularly favorable for heparan sulfate attachment. Comparison of leve ls 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 lamini n-binding domain. The high transcription levels in lung and kidney cor responded with the accumulation of agrin in the alveolar and glomerula r basement membranes, suggesting a filtration-associated function. The se data provide new directions for investigating the role of agrin in its different physiological environments, including the basement membr anes of the neuromuscular junction, kidney and lung.