The neuroendocrine proteins secretogranin II and III are regionally conserved and coordinately expressed with proopiomelanocortin in Xenopus intermediate pituitary.
Chromogranins and secretogranins are acidic secretory proteins of unknown function that represent major constituents of neuroendocrine secretary granules. Using a differential screening strategy designed to identify 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 Xenopus intermediate pituitary cDNA library. A comparative analysis of the Xenopus and mammalian proteins revealed a striking regional conservation with an overall sequence identity of 48% for SgII and 61% for SgIII. One of the highly conserved and thus potentially functional domains in 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 contains a conserved and repeated motif (DSTK) that is reminiscent of a repeat present in the trans-Golgi network integral membrane proteins TGN38 and TGN41, a finding more consistent with an intracellular function for this protein. When Xenopus intermediate pituitary cells were stimulated in vivo, the mRNA levels of SgII and SgIII increased dramatically (15- and 35-fold, respectively) and in parallel with that of the prohormone proopiomelanocortin (30-fold increase). Our results indicate that the process of peptide hormone production and release in a neuroendocrine cell involves multiple members of the granin family.
Holthuis
J C
JC
Department of Animal Physiology, University of Nijmegen, The Netherlands.
Martens
G J
GJ
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002864:Chromogranins; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D005786:Gene Expression Regulation / Q000502:physiology; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology; D014982:Xenopus laevis / Q000235:genetics*
D002864:Chromogranins; D018076:DNA, Complementary; D011506:Proteins; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin