THE NEUROENDOCRINE PROTEINS SECRETOGRANIN-II AND SECRETOGRANIN-III ARE REGIONALLY CONSERVED AND COORDINATELY EXPRESSED WITH PROOPIOMELANOCORTIN IN XENOPUS INTERMEDIATE PITUITARY

Chromogranins and secretogranins are acidic secretory proteins of unkn own function that represent major constituents of neuroendocrine secre tory granules. Using a differential screening strategy designed to ide ntify genes involved in peptide hormone biosynthesis and secretion, we have isolated cDNA clones encoding the first nonmammalian homologues of secretogranin II (SgII) and secretogranin III (SgIII) from a Xenopu s intermediate pituitary cDNA library. A comparative analysis of the X enopus and mammalian proteins revealed a striking regional conservatio n with an overall sequence identity of 48% for SgII and 61% for SgIII. One of the highly conserved and thus potentially functional domains i n SgII corresponds to the bioactive peptide secretoneurin. However, in SgII and especially in SgIII, a substantial portion of the potential dibasic cleavage sites is not conserved, arguing against the idea that these granins serve solely as peptide precursors, Moreover, SgIII con tains a conserved and repeated motif (DSTK) that is reminiscent of a r epeat present in the trans-Golgi network integral membrane proteins TG N38 and TGN41, a finding more consistent with an intracellular functio n for this protein. When Xenopus intermediate pituitary cells were sti mulated in vivo, the mRNA levels of SgII and SgIII increased dramatica lly (15- and 35-foId, respectively) and in parallel with that of the p rohormone proopiomelanocortin (30-fold increase). Our results indicate that the process of peptide hormone production and release in a neuro endocrine cell involves multiple members of the granin family.