In vitro translation of rabbit lung Clara cell secretory protein mRNA

The major secretory product of Clara cells is a low molecular weight protein (CCSP) whose extracellular function, at this time, is not known. The primary translation product of its mRNA is a protein with molecular weight approximately 1 kD greater than that of the native secreted protein (6.0 kD). The primary translation product is not detected in incubated lung tissue, only the secretory protein is found. The primary translation product is trypsin sensitive whereas the secretory protein is not. Cell free translation of the mRNA in the presence of microsomes results in cleavage of the signal peptide and the appearance of the lower molecular weight trypsin-resistant secretory protein. These data indicate that the low molecular weight Clara cell secretory protein is synthesized as a larger, trypsin sensitive, protein. Passage of the protein into the cisternae of the endoplasmic reticulum results in loss of the signal peptide and alterations to the tertiary structure of the protein rendering it trypsin insensitive.