GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma
NATURE GENETICS
Authors: Nord, Karolin H.; Lilljebjorn, Henrik; Vezzi, Francesco; Nilsson, Jenny; Magnusson, Linda; Tayebwa, Johnbosco; de Jong, Danielle; Bovee, Judith V. M. G.; Hogendoorn, Pancras C. W.; Szuhai, Karoly
Abstract
Glutamate receptors are well-known actors in the central and peripheral nervous systems, and altered glutamate signaling is implicated in several neurological and psychiatric disorders. It is increasingly recognized that such receptors may also have a role in tumor growth. Here we provide direct evidence of aberrant glutamate signaling in the development of a locally aggressive bone tumor, chondromyxoid fibroma (CMF). We subjected a series of CMFs to whole-genome mate-pair sequencing and RNA sequencing and found that the glutamate receptor gene GRM1 recombines with several partner genes through promoter swapping and gene fusion events. The GRM1 coding region remains intact, and 18 of 20 CMFs (90%) showed a more than 100-fold and up to 1,400-fold increase in GRM1 expression levels compared to control tissues. Our findings unequivocally demonstrate that direct targeting of GRM1 is a necessary and highly specific driver event for CMF development.
Variation in umami perception and in candidate genes for the umami receptor in mice and humans
AMERICAN JOURNAL OF CLINICAL NUTRITION
Authors: Shigemura, Noriatsu; Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, A. A. Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo
Abstract
The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5'-monophosphate and guanosine 5'-monophosphate. There is evidence that a heterodimeric G protein-coupled receptor, which consists of the T1R1 ( taste receptor type 1, member 1, Tas1r1) and the T1R3 ( taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR1 ( glutamate receptor, metabotropic 1, Grm1) and mGluR4 ( glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species. Am J Clin Nutr 2009; 90( suppl): 764S-9S.