Studies on the Very Large G Protein‑Coupled Receptor From Initial Discovery to Determining Its Role in Sensorineural Deafness in Higher Animals

Chapter Details

Pub Date: 28 Dec 2010
Pages: 11
Chapter Category: Cell Biology
Taken from the Book: Adhesion-GPCRs: Structure to Function
Book Series: Special Books
Edited by: Simon Yona and Martin Stacey

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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 and Perrin C. White

About this Chapter

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‑b 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.

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