A Mouse Photoreceptor Proteome Resource Identifies PALS2/MPP6 as a Novel Pan-Cone Photoreceptor Marker.

PURPOSE: To generate a quantitative proteome expression resource of rod and cone photoreceptors from the mouse retina that allows the exploration of cell type-specific proteomic landscapes. METHODS: Fluorescence-activated cell sorting of rod and cone photoreceptors was followed by in-solution digestion with trypsin using filter-aided sample preparation. Mass spectrometry analysis was performed using data-independent acquisition (DIA). RESULTS: Demonstrating the potential of our proteome resource, we identified PALS2 (protein associated with LIN7 2), also known as MPP6 (membrane palmitoylated protein 6), as a protein present in cone photoreceptors but absent in rod photoreceptors. We established PALS2/MPP6 as a novel pan-cone photoreceptor marker. Importantly, the high protein sequence coverage of DIA mass spectrometry allows one to gain deeper insights into photoreceptor type-specific protein isoforms. We show this with examples of PALS2/MPP6 and different synaptic proteins. CONCLUSIONS: Our quantitative proteome resource provides comprehensive details on the protein composition of mouse rod and cone photoreceptors and identifies PALS2/MPP6 as a novel pan-cone photoreceptor marker.