This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Han, L. Articles by Hosaka, M. Search for Related Content PubMed PubMed Citation Articles by Han, L. Articles by Hosaka, M.

A Large Form of Secretogranin III Functions as a Sorting Receptor for Chromogranin A Aggregates in PC12 Cells

Department of Molecular Medicine (L.H., M.S., R.W., T.T., M.H.) and Biosignal Research Center (Y.O.), Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan; Department of Neurophysiology, Gunma University Graduate School of Medicine (K.T., H.H.), Maebashi 371-8511, Japan; and Department of Anatomy II (T.W.), Asahikawa Medical College, Asahikawa 078-8510, Japan

Address all correspondence and requests for reprints to: Masahiro Hosaka, Secretion Biology Lab, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan. E-mail: mhosaka{at}showa.gunma-u.ac.jp.

Granin-family proteins, including chromogranin A and secretogranin III, are sorted to the secretory granules in neuroendocrine cells. We previously demonstrated that secretogranin III binds chromogranin A and targets it to the secretory granules in pituitary corticotrope-derived AtT-20 cells. However, secretogranin III has not been identified in adrenal chromaffin and PC12 cells, where chromogranin A is correctly sorted to the secretory granules. In this study, low levels of a large and noncleaved secretogranin III have been identified in PC12 cells and rat adrenal glands. Although the secretogranin III expression was limited in PC12 cells, when the FLAG-tagged secretogranin III lacking the secretory granule membrane-binding domain was expressed excessively, hemagglutinin-tagged chromogranin A was unable to target to the secretory granules at the tips and shifted to the constitutive secretory pathway. Secretogranin III was able to bind the aggregated form of chromogranin A, suggesting that a small quantity of secretogranin III is enough to carry a large quantity of chromogranin A. Furthermore, secretogranin III bound adrenomedullin, a major peptide hormone in chromaffin cells. Indeed, small interfering RNA-directed secretogranin III depletion impaired intracellular retention of chromogranin A and adrenomedullin, suggesting that they are constitutively released to the medium. We suggest that the sorting function of secretogranin III for chromogranin A is common in PC12 and chromaffin cells as well as in other endocrine cells, and a small amount of secretogranin III is able to sort chromogranin A aggregates together with adrenomedullin to secretory granules.

This article has been cited by other articles:

				K. Hotta, M. Hosaka, A. Tanabe, and T. Takeuchi Secretogranin II binds to secretogranin III and forms secretory granules with orexin, neuropeptide Y, and POMC J. Endocrinol., July 1, 2009; 202(1): 111 - 121. [Abstract] [Full Text] [PDF]

				M. Montero-Hadjadje, S. Elias, L. Chevalier, M. Benard, Y. Tanguy, V. Turquier, L. Galas, L. Yon, M. M. Malagon, A. Driouich, et al. Chromogranin A Promotes Peptide Hormone Sorting to Mobile Granules in Constitutively and Regulated Secreting Cells: ROLE OF CONSERVED N- AND C-TERMINAL PEPTIDES J. Biol. Chem., May 1, 2009; 284(18): 12420 - 12431. [Abstract] [Full Text] [PDF]

				P. Prasad, A. A. Yanagihara, A. L. Small-Howard, H. Turner, and A. J. Stokes Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A J. Immunol., October 1, 2008; 181(7): 5024 - 5034. [Abstract] [Full Text] [PDF]