An alternative amino-terminus expressed in the central nervous system converts agrin to a type II transmembrane protein

Neumann, Frank R. and Bittcher, Godela and Annies, Maik and Schumacher, Beat and Kroger, Stephan and Ruegg, Markus A.. (2001) An alternative amino-terminus expressed in the central nervous system converts agrin to a type II transmembrane protein. Molecular and cellular neuroscience, 17 (1). pp. 208-225.

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Agrin is a basal lamina-associated heparansulfate proteoglycan that is a key molecule in the formation of the vertebrate neuromuscular junction. The carboxy-terminal part of agrin is involved in its synaptogenic activity. The amino-terminal end of chick agrin consists of a signal sequence, required for the targeting of the protein to the secretory pathway, and the amino-terminal agrin (NtA) domain that binds to basal lamina-associated laminins. The cDNA encoding rat agrin lacks this NtA domain and instead codes for a shorter amino-terminal end. While the NtA domain is conserved in several species, including human, sequences homologous to the amino-terminus of rat agrin have not been described. In this work, we have characterized these amino-terminal sequences in mouse and chick. We show that they all serve as a noncleaved signal anchor that immobilizes the protein in a N(cyto)/C(exo) orientation in the plasma membrane. Like the secreted form, this transmembrane form of agrin is highly glycosylated indicative of a heparansulfate proteoglycan. The structure of the 5' end of the mouse agrin gene suggests that a distinct promoter drives expression of the transmembrane form. Agrin transcripts encoding this form are enriched in the embryonic brain, particularly in neurons. To our knowledge, this is the first example of a molecule that is synthesized both as a basal lamina and a plasma membrane protein.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A. and Neumann, Frank R.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Feb 2020 07:41
Deposited On:22 Mar 2012 13:20

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