Receptor Processing Sample Clauses

Receptor Processing. N-terminal fragments of GPR37L1 have been identified in human cerebral spinal fluid (CSF), suggesting the processing of GPR37L1 may be biologically relevant (Xxxxx et al. 2001; Zhao et al. 2010). Interestingly, while GPR37 and GPR37L1 have predicted molecular weights of 67 and 53kDa respectively, the predominant form of both receptors detected following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is roughly 20kDa below their predicted sizes (Imai et al. 2001; Rezgaoui et al. 2006; Marazziti et al. 2007; Omura et al. 2008; Xxxxxxx, Tuusa, and Petaja-Repo 2016; Xxxxxxx et al. 2016). Immunodetection with C-terminal antibodies suggests the main form of the receptor is N-terminally cleaved. Endothelin B (ETB), the most closely related neighbor to GPR37 and GPR37L1 is also known to undergo N-terminal cleavage. Studies with N-terminally truncated forms of ETB show reduced surface expression, suggesting receptor processing may regulate surface expression (Xxxxxxxxxxxx et al. 2002). Similar studies with an N-terminally truncated form of GPR37 indicate truncated versions of the receptor display increased surface expression (Xxxxxx et al. 2009; Xxxxxxx, Tuusa, and Petaja-Repo 2016). Expression of GPR37 modified to contain dual epitope tags at the N and C termini, clearly demonstrate the existence of several differentially sized versions of the receptor (Xxxxxxx, Tuusa, and Petaja-Repo 2016). The most abundantly expressed form was detected at 53kDa and contained only the CT epitope tag, suggesting an N-terminally truncated form of the receptor. Pulse-chase labeling of HEK cells stably-transfected with GPR37, reveals that cleavage of the receptor occurs after processing of receptor N-glycans in the Golgi (Xxxxxxx, Tuusa, and Petaja-Repo 2016). Co-localization with endocytic markers indicate that GPR37 is cleaved only after it leaves the trans-Golgi network. Additionally, broad-range metalloproteinase inhibitors, GM6001, TAPI-1 and marimastat prevent GPR37 cleavage and increase the amount of full-length receptor at the cell surface (Xxxxxxx, Tuusa, and Petaja-Repo 2016). The functional role of GPR37 cleavage has yet to be investigated. Xxxxxxx and colleagues (Xxxxxxx et al. 2016) set out to determine the functional significance of GPR37L1 N-terminal cleavage. In contrast to GPR37, removal of the N-terminus of GPR37L1 reduces total and surface expression. Furthermore, truncation of the NT completely abolished GPR37L1’s constitutive signaling to C...