Fig. 1

Drosophila CASK gene, proteins, and genetic reagents. a Color-coded schematic, drawn to scale, showing identical organization of CASK protein domains in H. sapiens and D. melanogaster. Amino-acid (aa) sequence similarity (%) as indicated; identities are CaMK-like 68%; L27A 31%; L27B 45%; PDZ 82%; SH3 67%; GUK 70%. The white boxes between SH3 and GUK are the "hook" motif. b Cytogenetic and molecular maps of CASK (FlyBase ID FBgn0013759; https://flybase.org/reports/FBgn0013759, last accessed 6 February 2023). Region 93F10-12 on right arm of chromosome 3 [86], reproduced in [91], centromere to the left. CASK gene span: genomic DNA map 21,783 – 21,822 kb (Fly Base, FB2022_06); scale at top right applies to all maps in (b)-(d). Protein orientation in (a) is flipped 180° relative to transcription direction. CASK (blue), with two transcriptional start sites (left-pointing arrows), and tsl (green) genes. P-element EY07081 insertion site in first intron. Two overlapping chromosomal deficiencies delete CASK DNA, with breakpoints estimated by restriction mapping [96]. c CASK alleles [142]. Imprecise excision of EY07081 generated CASK mutation, ∆18, with deletion of exons 1 and 2, and insertion of small piece of roo transposon at the breakpoint. Precise excision yielded Ex33, which serves as the control allele. (d) Endogenous and engineered CASK transcripts. Boxes represent exons; color scheme for encoded protein domains as in (a), gray for 5'- and 3'-untranslated regions. CASK-β is the full-length transcript; internal promoter generates short transcript, CASK-α, which is missing the 5' exons. The UAS-CASK⁺ 10.20 construct expresses full-length wild-type CASK cDNA under UAS control