Alternatively spliced mRNA molecules of the thrombospondin receptor (CD36) in human PBMC

We employed reverse transcription polymerase chain reaction (RT-PCR) to detect alternatively spliced CD36 mRNA in human peripheral blood mononuclear cells (PBMC). Sequencing of cloned cDNA revealed alternatively spliced mRNA molecules in 13 out of 39 clones. We observed exon skipping of up to 10 out of 12 coding exons in eight alternative transcripts. Additionally, in five of the transcripts, alternative splice donor or acceptor sites were used during mRNA maturation. Considering the CD36 molecule serves many functions in coagulation, host defence, lipid metabolism, and scavenging, we speculate that the proteins encoded by the alternatively spliced mRNA molecules may be involved in regulation of both CD36 gene expression and function. The human CD36 molecule is a 78-88 kDa glycoprotein belonging to the class B scavenger receptor (SR) gene family (Endemann et al., 1993). In humans the gene has been localized to chromosome 7 (7q11.2 band) (Fernandez-Ruiz et al., 1993). The protein has two hydrophobic amino acid domains. located at both the carboxy and the amino terminals. Soluble carboxy-terminal truncation mutants binding to thrombospondin showed evidence for a single transmembrane region (carboxy-terminal) (Pearce et al., 1994). However; controversial data (Tao et al., 1996) suggest the amino terminal hydrophobic region is associated with the outer surface of the cytoplasmic membrane. Six carboxy-terminal amino acids are reported to be located in the cytoplasm (Vega et al., 1991). If there were a second amino terminal transmembrane region, another six amino acids would be located in the cytoplasm. The single large extracellular domain contains most of the potential N-glycosylation sites in its amino-terminal region, whereas the carboxy-terminal region is rich in conserved proline, glycine and cysteine residues (Greenwalt et al., 1992).