Letter | Published:

Re-routing of a secretory protein by fusion with human growth hormone sequences

Nature volume 321, pages 443446 (22 May 1986) | Download Citation

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Abstract

Cells with electron-dense secretory vesicles use them to store only specialized secretory products such as peptide hormones; other types of secreted proteins are externalized by an alternative, constitutive route1. One possible mechanism for such segregation is that proteins destined for dense secretory vesicles contain unique ‘sorting domains’2 that allow for selective targeting. Here, we set out to determine whether a constitutively secreted protein could be diverted to the dense secretory vesicles by attachment to a peptide hormone sequence. We made use of the ability of the mouse pituitary tumour cell line, AtT-20, to correctly sort exogenous secretory proteins introduced into them by DNA transfection3. We constructed a plasmid encoding a hybrid protein in which a constitutively secreted viral protein was fused to the carboxy terminus of human growth hormone (hGH). Cells expressing the hybrid protein were found to target it to dense secretory vesicles with an efficiency close to that observed for the parental hGH. These results support the hypothesis that sorting domains on peptide hormones direct their packaging into dense secretory vesicles. The results also suggest that proteins secreted by the constitutive pathway either do not contain any sorting domain, or their sorting signals can be overridden by those which direct peptide hormones.

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Author information

Affiliations

  1. Department of Physiology-Anatomy, University of California, Berkeley, California 94720, USA

    • Hsiao-ping H. Moore
  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA

    • Regis B. Kelly

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DOI

https://doi.org/10.1038/321443a0

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