RGA protein associates with a TRPV ion channel during biosynthesis and trafficking

Abstract

TRPV ion channels transduce a range of temperature stimuli. We proposed that analysis of the protein-protein interactions made by TRPV2 might give insight into the key issues surrounding this channel. These issues include the potential functional significance of TRPV2 in non-sensory tissues, the molecules involved in transducing its activation signal(s) and the mechanism by which its trafficking to the cell surface is regulated. Here we describe the interaction of TRPV2 channel with the RGA gene product. RGA is a four-transmembrane domain, intracellularly localized protein. RGA associates with TRPV2 in a rat mast cell line that is a native context for both proteins. The interaction between TRPV2 and RGA is transient and occurs intracellularly. RGA does not accompany TRPV2 to the cell surface. Formation of the TRPV2/RGA complex is dependent upon a cellular glycosylation event, suggesting that RGA may play a chaperone or targeting role for TRPV2 during the maturation of the ion channel protein. These data record a novel protein-protein interaction for TRPV2 and provide a foundation for future study of the potential regulatory contribution of RGA to TRPV2 function.

The Bacterial Pathogen Xanthomonas oryzae Overcomes Rice Defenses by Regulating Host Copper Redistribution

“…For example, coexpression of fission yeast SpCtr4 and SpCtr5 is required for complementation of S. cerevisiae ctr mutant or S. pombe ctr mutant because the two proteins are interdependent for trafficking to the plasma membrane and form a heteromeric complex for mediating a highaffinity Cu transport; S. pombe Ctr5 is also required for Ctr4 folding (Zhou and Thiele, 2001;Beaudoin et al, 2006). The rat plasma membrane-localized ion channel protein TRPV2 interacts with the endoplasmic reticulum/Golgi apparatus-localized RGA protein; RGA plays role in trafficking of TRPV2 to plasma membrane (Barnhill et al, 2004;Stokes et al, 2005). The RGA is suggested to have four transmembrane regions and is distantly related to the MtN3/saliva-type proteins (Stokes et al, 2005).…”

RUPTURED POLLEN GRAIN1, a Member of the MtN3/saliva Gene Family, Is Crucial for Exine Pattern Formation and Cell Integrity of Microspores in Arabidopsis

“…Recently, the Rga protein was revealed to be associated with the ion channel protein TRPV2 in a rat mast cell line (Barnhill et al, 2004;Stokes et al, 2005). TRPV2 is a member of the TRPV (vanilloid receptorrelated) subfamily of the TRP (for Transient Receptor Potential) family.…”

TRPC1-mediated Inhibition of 1-Methyl-4-phenylpyridinium Ion Neurotoxicity in Human SH-SY5Y Neuroblastoma Cells

“…Targeting of TRP proteins to the plasma membrane is essential for its function, which is dependent on its ability to interact with other proteins. TRPC1 interaction with caveolin 1 and TRPV2 interaction with a chaperone protein RGA is critical for their trafficking to the plasma membrane (28,29). Further, TRPC3, TRPC5, and TRPC6 have been shown to be present in vesicles and are translocated to the membrane upon stimulation (30,31).…”