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

14 Citations (Scopus)

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 publicationAdvances in Experimental Medicine and Biology
Pages76-86
Number of pages11
Volume706
DOIs
StatePublished - 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume706
ISSN (Print)00652598

Fingerprint

Deafness
G-Protein-Coupled Receptors
Animals
Deaf-Blind Disorders
Usher Syndromes
Ligands
Mutation
Cytoskeletal Proteins
Cochlea
Adhesion
Hearing Loss
Open Reading Frames
Epilepsy
Consensus
Membrane Proteins
Seizures
Audition
Calcium
Defects
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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 Advances in Experimental Medicine and Biology (Vol. 706, pp. 76-86). (Advances in Experimental Medicine and Biology; Vol. 706). https://doi.org/10.1007/978-1-4419-7913-1_6

Studies on the very large G protein-coupled receptor : From initial discovery to determining its role in sensorineural deafness in higher animals. / McMillan, D. Randy; White, Perrin C.

Advances in Experimental Medicine and Biology. Vol. 706 2010. p. 76-86 (Advances in Experimental Medicine and Biology; Vol. 706).

Research output: Chapter in Book/Report/Conference proceedingChapter

McMillan, DR & White, PC 2010, Studies on the very large G protein-coupled receptor: From initial discovery to determining its role in sensorineural deafness in higher animals. in Advances in Experimental Medicine and Biology. vol. 706, Advances in Experimental Medicine and Biology, vol. 706, pp. 76-86. https://doi.org/10.1007/978-1-4419-7913-1_6
McMillan DR, White PC. Studies on the very large G protein-coupled receptor: From initial discovery to determining its role in sensorineural deafness in higher animals. In Advances in Experimental Medicine and Biology. Vol. 706. 2010. p. 76-86. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-1-4419-7913-1_6
McMillan, D. Randy ; White, Perrin C. / Studies on the very large G protein-coupled receptor : From initial discovery to determining its role in sensorineural deafness in higher animals. Advances in Experimental Medicine and Biology. Vol. 706 2010. pp. 76-86 (Advances in Experimental Medicine and Biology).
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