Studies on the very large G protein-coupled receptor: From initial discovery to determining its role in sensorineural deafness in higher animals

D. Randy McMillan, Perrin C. White

Research output: Chapter in Book/Report/Conference proceedingChapter

16 Scopus citations

Abstract

The very large G protein-coupled receptor 1 (VLGR1), also known as MASS1 or GPR98, is most notable among the family of adhesion-GPCR for its size. Encoded by an 18.9 kb open reading frame, the ∼700 kDa primary translation product is by far the largest GPCR and additionally, the largest cell surface protein known to date. The large ectodomain of the protein contains several repeated motifs, including some 35 calcium binding, Calx-β repeats and seven copies of an epitempin repeat thought to be associated with the development of epilepsy. The extreme carboxy-terminus contains a consensus PDZ ligand sequence, suggesting interactions with other cytosolic or cytoskeletal proteins. At least two spontaneous and two targeted mutant mouse lines are currently known. The mutant mice present with sensitivity to audiogenic seizures but also have cochlear defects and significant, progressive hearing impairment. Although its ligand is currently unknown, VLGR1 is one of the few adhesion-GPCR family members in which mutations have been shown to be responsible for a human malady. Mutations in VLGR1 in humans result in one form (2C) of Usher syndrome, the most common genetic cause of combined blindness and deafness.

Original languageEnglish (US)
Title of host publicationAdhesion-GPCRs
Subtitle of host publicationStructure to Function
EditorsSimon Yona, Martin Stacey
Pages76-86
Number of pages11
DOIs
StatePublished - Dec 1 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume706
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    McMillan, D. R., & White, P. C. (2010). Studies on the very large G protein-coupled receptor: From initial discovery to determining its role in sensorineural deafness in higher animals. In S. Yona, & M. Stacey (Eds.), Adhesion-GPCRs: Structure to Function (pp. 76-86). (Advances in Experimental Medicine and Biology; Vol. 706). https://doi.org/10.1007/978-1-4419-7913-1_6