Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway.

Abstract

We report on the biochemical and immunological properties as well as on the cellular and subcellular distribution of two proteins, called secretogranins I and II. These proteins specifically occur in a wide variety of endocrine and neuronal cells that package and sort regulatory peptides into secretory granules. Both secretogranins take the same intracellular route as the peptides and are also sorted into secretory granules. Secretogranins I and II are biochemically and immunologically distinct proteins and differ from chromogranin A. Yet, these three proteins are similar to each other in many respects and therefore constitute one class of proteins. A remarkable feature of this protein class is a very acidic pI, brought about by a high content of acidic amino acids as well as by phosphorylation on serine and sulfation on tyrosine and O-linked carbohydrate. As a result, this class of proteins has a high net negative charge even at the acidic pH of the trans Golgi cisternae. We discuss the possibility that this property of the proteins may point to a role in the packaging of regulatory peptides into secretory granules.

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

“…Such staining could also be seen with chromaffin granules when higher protein amounts were applied (results not shown). It has already been established that this band corresponds to a special form of chromogranin A, containing highly sulfated proteoglycan chains (Falkensammer et al 1985b;Rosa et al 1985). Figure 1 demonstrates that the pancreas contains a relatively high concentration of this special form of chromogranin A.…”

“…Boiling enriches the heat-stable chromogranins/secretogranins (Rosa et al 1985) and in addition is efficient in preventing proteolytic degradation. Fetal pancreas was used since before birth the endocrine tissue represents a relatively high proportion of this organ.…”

“…Concerning the additional immunoreactive bands differences have been observed between adrenal medulla and the pancreas. In the latter organ a relatively large amount of a higher molecular weight form of chromogranin A is present probably representing a proteoglycan (Rosa et al 1985;Falkensammer et al 1985). In addition, the endocrine pancreas contained a significant amount of a smaller component of secretogranin II which was apparently absent from adrenal medulla.…”

“…The supernatant was centrifuged for 1 h at 100000 • ga~-The pellet was resuspended in water (tenfold volume), boiled for 5 rain and spun down for 10 min at 2500 • g~y. This procedure increases the yield of heat stable chromogranins/secretogranins (Rosa et al 1985) and prevents proteolytic artifacts. The lyophilized supernarant was used for the electrophoresis.…”

“…Chromogranin A and B and secretogranin II are widely distributed in endocrine tissues (Cohn et al 1982;O'Connor 1983;Wilson and Lloyd 1984;Rindi et al 1986;Lassmann et al 1986;Rosa et al 1985) and all three antigens have been demonstrated immunohistochemically in the endocrine pancreas of several species Lloyd et al 1984; Fischer-* To whom offprint requests should be sent Lassmann et al 1986;Hagn et al 1986;Rindi et al 1986).…”