Journal Article

The epilepsy gene <i>LGI1</i> encodes a secreted glycoprotein that binds to the cell surface

Maria Salomé Sirerol-Piquer, Ana Ayerdi-Izquierdo, José Manuel Morante-Redolat, Vicente Herranz-Pérez, Kristy Favell, Philip A. Barker and Jordi Pérez-Tur

in Human Molecular Genetics

Volume 15, issue 23, pages 3436-3445
Published in print December 2006 | ISSN: 0964-6906
Published online October 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl421
The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface

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Autosomal dominant lateral temporal epilepsy (ADTLE) is a partial epilepsy caused by mutations in LGI1, a multidomain protein of unknown function. To begin to understand the biological function of LGI1, we have determined its pattern of glycosylation, subcellular expression and capacity for secretion. LGI1 is expressed as two different isoforms in the brain, and we show that the long isoform is a secreted protein, whereas the short isoform is retained in an intracellular pool. ADLTE-related mutants of the long form are defective for secretion and are retained in the endoplasmic reticulum and Golgi complex. Finally, we show that normal secreted LGI1 specifically binds to the cell surface of differentiated PC12 cells. We propose that LGI1 is a secreted factor important for neuronal development and that ADTLE is a disease that results from the loss of regulation in the protein available either extracellular or intracellularly.

Journal Article.  5311 words.  Illustrated.

Subjects: Genetics and Genomics

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