Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis.

PloS One
Victoria E AbrairaLisa V Goodrich

Abstract

The Lrig genes encode a family of transmembrane proteins that have been implicated in tumorigenesis, psoriasis, neural crest development, and complex tissue morphogenesis. Whether these diverse phenotypes reflect a single underlying cellular mechanism is not known. However, Lrig proteins contain evolutionarily conserved ectodomains harboring both leucine-rich repeats and immunoglobulin domains, suggesting an ability to bind to common partners. Previous studies revealed that Lrig1 binds to and inhibits members of the ErbB family of receptor tyrosine kinases by inducing receptor internalization and degradation. In addition, other receptor tyrosine kinase binding partners have been identified for both Lrig1 and Lrig3, leaving open the question of whether defective ErbB signaling is responsible for the observed mouse phenotypes. Here, we report that Lrig3, like Lrig1, is able to interact with ErbB receptors in vitro. We examined the in vivo significance of these interactions in the inner ear, where Lrig3 controls semicircular canal formation by determining the timing and extent of Netrin1 expression in the otic vesicle epithelium. We find that ErbB2 and ErbB3 are present in the early otic epithelium, and that Lrig3 acts cell-autono...Continue Reading

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Citations

Sep 4, 2014·Endocrine-related Cancer·Catalina SimionColleen Sweeney
Apr 25, 2012·Journal of the Association for Research in Otolaryngology : JARO·Brandon C CoxJian Zuo
Sep 3, 2014·Acta Oncologica·David LindquistHåkan Hedman
Feb 25, 2015·Journal of the Neurological Sciences·Dongsheng GuoTing Lei
Mar 17, 2016·Journal of the Association for Research in Otolaryngology : JARO·Kevin K OhlemillerPatricia M Gagnon
Aug 31, 2017·Development·Allison M NishitaniLisa V Goodrich
Mar 5, 2016·EMBO Reports·Fernando Cruz AlsinaGustavo Paratcha
Mar 25, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Martin HellströmHåkan Hedman
Jan 22, 2021·Seminars in Cancer Biology·Yibing JiDean G Tang

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Methods Mentioned

BETA
ubiquitination
co-immunoprecipitations
dissection
PCR

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