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Related Experiment Videos

Trafficking/sorting and granule biogenesis in the beta-cell.

M Molinete1, J C Irminger, S A Tooze

  • 1Louis-Jeantet Research Laboratories, University Medical Center, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.

Seminars in Cell & Developmental Biology
|September 1, 2000
PubMed
Summary

Newly formed secretory granules in beta-cells package proinsulin via an elusive sorting mechanism. Granule maturation involves clathrin loss and acidification, refining contents for insulin production.

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Area of Science:

  • Cell biology
  • Endocrinology
  • Molecular biology

Background:

  • Proinsulin is synthesized in the trans-Golgi network (TGN) of pancreatic beta-cells.
  • Packaging into secretory granules involves sorting of proinsulin and conversion enzymes.
  • The precise mechanism of this sorting process remains largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of proinsulin sorting into nascent secretory granules.
  • To understand the role of clathrin and granule maturation in content refinement.

Main Methods:

  • Observation of secretory granule formation and maturation in beta-cells.
  • Analysis of protein sorting and clathrin dynamics during granule development.

Main Results:

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  • Proinsulin and conversion enzymes are packaged into immature, clathrin-coated granules.
  • Granule maturation involves clathrin coat loss and acidification.
  • Clathrin-coated vesicles bud from maturing granules, refining granular content.

Conclusions:

  • Proinsulin packaging relies on an active sorting mechanism in the TGN.
  • Granule maturation, including clathrin loss, is crucial for refining secretory products.
  • This process ensures efficient conversion of proinsulin to insulin and C-peptide.