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A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands.

ABSTRACT: Notch signaling affects many developmental and cellular processes and has been implicated in congenital disorders, stroke, and numerous cancers. The Notch receptor binds its ligands Delta and Serrate and is able to discriminate between them in different contexts. However, the specific domains in Notch responsible for this selectivity are poorly defined. Through genetic screens in Drosophila, we isolated a mutation, Notch(jigsaw), that affects Serrate- but not Delta-dependent signaling. Notch(jigsaw) carries a missense mutation in epidermal growth factor repeat-8 (EGFr-8) and is defective in Serrate binding. A homologous point mutation in mammalian Notch2 also exhibits defects in signaling of a mammalian Serrate homolog, Jagged1. Hence, an evolutionarily conserved valine in EGFr-8 is essential for ligand selectivity and provides a molecular handle to study numerous Notch-dependent signaling events.

SUBMITTER: Yamamoto S 

PROVIDER: S-EPMC3663443 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands.

Yamamoto Shinya S   Charng Wu-Lin WL   Rana Nadia A NA   Kakuda Shinako S   Jaiswal Manish M   Bayat Vafa V   Xiong Bo B   Zhang Ke K   Sandoval Hector H   David Gabriela G   Wang Hao H   Haltiwanger Robert S RS   Bellen Hugo J HJ  

Science (New York, N.Y.) 20121101 6111

Notch signaling affects many developmental and cellular processes and has been implicated in congenital disorders, stroke, and numerous cancers. The Notch receptor binds its ligands Delta and Serrate and is able to discriminate between them in different contexts. However, the specific domains in Notch responsible for this selectivity are poorly defined. Through genetic screens in Drosophila, we isolated a mutation, Notch(jigsaw), that affects Serrate- but not Delta-dependent signaling. Notch(jig  ...[more]