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Protein Hormone Storage in Secretory Granules: Mechanisms for Concentration and Sorting¹

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

I. Introduction: Concentrating Protein Hormones in Secretory Granules

II. A Well Characterized Sorting Mechanism: Lysosomal Hydrolases

A. Sorting is linked to transport

B. Specific transport is associated with specific vesicles

III. Sorting of Soluble Transported Proteins in the Endoplasmic Reticulum

A. Sorting in yeast

B. Sorting in mammalian cells

C. Implications for sorting into granules

IV. Two Models for the Functioning of the Golgi Complex

A. Vesicular transport of proteins vs. maturation of stacks

B. Implications for sorting into granules

V. Models for Formation of Secretory Granules

A. Active budding off of secretory granules vs. active budding off of everything else

B. Implications for sorting into granules

VI. Hormone Aggregates in Cells

A. Evidence for their existence

B. Properties of hormone aggregates in cells

VII. Hormone Aggregates in Solution

VIII. Does Aggregation Cause Sorting in Cells?

A. Ways to measure sorting

B. Does sorting in cells correlate with aggregation in solution?

IX. What Keeps Secretory Proteins from Aggregating?

X. Sorting in the trans-Golgi Network

A. Transmembrane proteins

B. Soluble proteins

XI. Sorting Signals and Sorting Signal Receptors for Secretory Granules

XII. All Secretory Granule Proteins Are Not Treated Equally

XIII. Summary.

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