Chromogranins: Universal proteins in secretory organelles from paramecium to man

The immunological approach to chromaffin granule research in the mid 1960s led to the discovery of the coexistence and cosecretion of chromogranins with catecholamine hormones and adenine nucleotides. Now three members of the chromogranin family of uniquely acidic proteins have been described; they are chromogranin A, B and C (secretogranin II), which are distributed in neurons, neuroendocrine and endocrine cells, in normal and neoplastic tissue. The chromogranins are postulated to serve not only as prohormones but also as crucial components of the core structure in the secretory organelles. Their role in costorage with biogenic amines, nucleotides, divalent metals and precursors for bioactive polypeptides remains an unsolved question. Proteolytic processing of the chromogranins leads to tissue-specific molecular heterogeneity of immunologically related cleavage products, of possible relevance for the condensation into protein lattices. The Donnan osmotic forces arising from the structured polyanion may in turn account for the accumulation of the hyperosmolar concentrations of small ions into isoosmolar states without complex formation between the small ions themselves. A condenser role for proteolytically processed, non-glycosylated chromogranin A in non-aminergic polypeptide secreting trichocysts of protozoa (Paramecium) suggests that the chromogranins may account for one of several strategies in the evolution of universal core structures for secretory organelles.