Alternative splicing, expression, and genomic structure of the 3 ' region of the gene encoding the sarcolemmal-associated proteins (SLAPs) defines a novel class of coiled-coil tail-anchored membrane proteins

The sarcolemmal associated proteins (SLAPs) are encoded by multiple mRNAs t hat are presumably generated by alternative splicing mechanisms. The amino acid sequence of the SLAP1 isoform exhibited 76% identity with TOP,, a topo graphically graded antigen of the chick visual system. The regions of coile d-coil structure including an Il-heptad acidic amphipathic alpha -helical s egment was conserved with a major divergence in sequence noted in the hydro phobic C termini predicted to be transmembrane domains in the two polypepti des. The genomic organization of the 3' region of the SLAP gene indicated t hat SLAP1 and TOP, are generated by alternative splicing mechanisms, which are conserved among mammalian and avian species. SLAP1/TOPAP were encoded b y II exons distributed over a minimum of 35 kilobase pairs of continuous DN A; 9 of the exons were constitutively expressed, and 2 were alternatively s pliced. The exons range in size from 60 to 321 base pairs, and the predicte d functional domains within the polypeptides were encompassed by single exo ns, The introns vary from 0.2 to 10 kilobase pairs and conform to consensus dinucleotide splicing signals. Reverse transcriptase-polymerase chain reac tion studies demonstrated that alternative exons (IV and X) of SLAP were ex pressed in a tissue-specific fashion and developmentally regulated. The alt ernatively spliced exon X, which encodes the putative transmembrane anchor in TOPAP, and a constitutively expressed exon XI, which encodes the putativ e transmembrane domain in SLAP, were found to target these polypeptides to membrane structures. The presence and conservation of termination codons in exons X and XI render expression of the two SLAP1/TOPAP transmembrane doma ins mutually exclusive. These data reveal that TOP, and SLAP are alternativ ely spliced products of a single gene that encodes a unique class of tail-a nchored membrane proteins.