TLS interaction with NMDA R1 splice variant in retinal ganglion cell line RGC-5.

Translocated in liposarcoma (TLS or FUS) is a multifunctional protein component of the heterogenous ribonuclear complex involved in the splicing of pre-mRNA and the export of fully processed mRNA from the nucleus to the cytoplasm. As we determined that TLS was substantially expressed in the adult retina, we investigated the functions of TLS in a rat retinal ganglion cell (RGC) line RGC-5. TLS was found to be associated with N-methyl-d-aspartate (NMDA) receptor 1 (NR1) and myosinVa (MyoVa) in a calcium-dependent manner. We demonstrated that TLS-associated NR1 could be one of the NR1 alternative splice variants, NR1-4, which was predominantly expressed in RGC-5. The degree of colocalization between TLS and NR1 was significantly decreased by depolarization of RGC-5 cells, indicating that the depolarization-induced Ca(2+)-influx triggered a redistribution of NR1 from the TLS-protein complex. These results suggested that TLS might be involved in a calcium-dependent trafficking of specific NR1 splice variants in RGCs.

Duke Scholars

Author Fulton Wong Ophthalmology