Download this chapter
Note: To save this PDF please
right-click, ctl-click on a Mac,
and select the "Save Link As"
option.
Share on Facebook
-
Chapter Category: Cell Biology
From the book Adhesion-GPCRs: Structure to Function
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
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.
- ISBN: 978-1-4419-7912-4
- Publication date: December 28, 2010
- Series: Special Books
Adhesion-GPCRs: Structure to Function
Edited by: Simon Yona and Martin Stacey
More chapters from the book:
GPR56 is a relatively recent addition to the adhesion‑GPCR family. Genetic and biochemical studies uncovered its roles in cancer and development and established its function as an adhesion receptor to mediate the interactions between cells and extracellular matrix. Despite of much progress...
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. WhiteThe 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...
Tumor growth is a highly complex, multistep process that involves tumor cell detachment, migration, invasion and metastasis accompanied by angiogenesis and extracellular matrix turn‑over. Each of the steps is influenced by tumor cell interaction and interaction of the tumor cell with its...
CD97 in Leukocyte Trafficking
Jörg Hamann, Henrike Veninga, Dorien M. de Groot, Lizette Visser, Claudia L. Hofstra, Paul P. Tak, Jon D. Laman, Annemieke M. Boots and Hans van EnennaamCD97 is a member of the EGF‑TM7 family of adhesion G protein‑coupled receptors (GPCRs) broadly expressed on leukocytes. CD97 interacts with several cellular ligands via its N‑terminal epidermal growth factor (EGF)‑like domains. To understand the biological function of CD97, monoclonal...
The stability and functional diversity of proteins can be greatly modulated by posttranslational modification. Proteolytic cleavage at the GPCR proteolysis site (GPS) has been identified as an intrinsic protein modification process of many adhesion‑GPCRs. In recent years, the conserved...
Understanding the mechanisms that coordinate the polarity of cells and tissues during embryogenesis and morphogenesis is a fundamental problem in developmental biology. We have recently demonstrated that the putative neurotoxin receptor lat‑1 defines a mechanism required for the alignment of...
The 7TM‑Cadherins, Celsr/Flamingo/Starry night, represent a unique subgroup of adhesion‑GPCRs containing atypical cadherin repeats, capable of homophilic interaction, linked to the archetypal adhesion‑GPCR seven‑transmembrane domain. Studies in Drosophila provided a first glimpse of...
Latrophilin, a neuronal “adhesion‑G protein‑coupled receptor”, is the major brain receptor for α‑latrotoxin, a black widow spider toxin which stimulates strong neuronal exocytosis in vertebrates. Latrophilin has an unusual structure consisting of two fragments that are produced by...
The male reproductive tract expresses a diverse array of adhesion‑GPCRs, many in a highly specific and regulated manner. Despite this specificity of expression, little is known about the function of this receptor family in male reproductive physiology. Insights into function are beginning to...
The Adhesion GPCRs; Gene Repertoire, Phylogeny and Evolution
Helgi B. Schiöth, Karl J. V. Nordström and Robert FredrikssonThe Adhesion family is unique among the GPCR (G protein‑coupled receptor) families because of several features including long N‑termini with multiple domains. The gene repertoire has recently been mined in great detail in several species including mouse, rat, dog, chicken and the early...
The signaling cascade of most adhesion‑GPCRs remains uncharacterized, as the majority are still orphan receptors and further complicated by their unique structure containing a cleaved long extracellular domain (ECD) and a seven‑transmembrane domain (7TM). In this chapter, we review...
As a macrophage‑restricted reagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF‑TM7 member of the adhesion‑GPCR...
CD97 was identified as an early activation marker on T cells, having low expression on naive T cells. This is a common feature of molecules that have a role in T‑cell function. It was subsequently identified as a ligand for CD55, which has been previously identified as an innate regulator of...
There are a total of 33 members of adhesion G protein‑coupled receptors (GPCRs) in humans and 30 members in mice and rats. More than half of these receptors are expressed in the central nervous system (CNS), indicating their possible roles in the development and function of the CNS. Indeed,...
Brain‑specific angiogenesis inhibitor 1 (BAI1) encodes a seven‑transmembrane protein that belongs to the adhesion‑GPCR family.1‑7 Although BAI1 was named for the ability of its extracellular region to inhibit angiogenesis in tumor models, its function in physiological contexts was...
Adhesion‑GPCRs are unusual, owing to their unique structure, comprising a large and complex extracellular domain composed of various common protein modules. Adhesion‑GPCR family members are expressed ubiquitously; however the expression of each receptor is highly regulated and often...