Extended Data Fig. 2: Alternative splicing of Lphn1 (Adgrl1), Lphn2 (Adgrl2), and regulation of Lphn1 and Lphn2 G-protein coupling by alternative splicing.

a & b, Schematic of Lphn1 (Adgrl1) (a) and Lphn2 (Adgrl2) (b) alternative splicing with a depiction of the amino acid sequences of some of the resulting variants (asterisk = stop codon). c & d, Analysis of a long-read PacBio sequencing dataset¹⁶ also reveals extensive combinatorial alternative splicing of Lphn1 and Lphn2 mRNAs. Reads are depicted as heatmaps (green boxes = Included exons; light grey boxes = excluded exons; asterisks = alternatively spliced exon). Each row represents a splice variant combination whose abundance is shown on the right (only the most abundant variants are shown). e, G-protein coupling preferences of two Lphn1 and Lphn2 splice variants revealed by TRUPATH analyses. The constitutive G-protein coupling strength (represented by the NET BRET signal) of the indicated Lphn1 and Lphn2 isoform were measured by TRUPATH assay in HEK293 cell. Splice variants with indicated spliced-in exons are shown. BRET signals at 300 ng receptor-transfected condition were normalized to the 0 ng transfected baseline. Graphs show means ± SEM from independent experiments (n = 3).