Abstract

Although much has been learned concerning the mechanisms of secretory vesicle formation and fusion at donor and acceptor membrane compartments, relatively little attention has been paid toward understanding how cells maintain a homeostatic membrane balance through vesicular trafficking. In neurons and neuroendocrine cells, release of neurotransmitters, neuropeptides, and hormones occurs through calcium-regulated exocytosis at the plasma membrane. To allow recycling of secretory vesicle components and to preserve organelles integrity, cells must initiate and regulate compensatory membrane uptake. This review relates the fate of secretory granule membranes after full fusion exocytosis in neuroendocrine cells. In particular, we focus on the potential role of lipids in preserving and sorting secretory granule membranes after exocytosis and we discuss the potential mechanisms of membrane retrieval.

Highlights

  • Mammalian cells exhibit complex and dynamic patterns of intracellular membrane traffic between various organelles

  • Using electron microscopy of cultured chromaffin cells, our group has recently described clustering of secretory granule proteins on the plasma membrane after full fusion exocytosis, arguing against the idea that granule components are dispersed in the plasma membrane [12]

  • HOW TO RECAPTURE A LARGE DENSE CORE VESICLE? In chromaffin cells, we have found that clathrin is rapidly recruited to the granule membrane right after merging with the plasma membrane and that knocking-down clathrin expression drastically blocks compensatory endocytosis [12]

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Summary

INTRODUCTION

Mammalian cells exhibit complex and dynamic patterns of intracellular membrane traffic between various organelles. Using electron microscopy of cultured chromaffin cells, our group has recently described clustering of secretory granule proteins on the plasma membrane after full fusion exocytosis, arguing against the idea that granule components are dispersed in the plasma membrane [12]. Secretagogue-evoked stimulation of chromaffin cells triggers the formation of lipid raft microdomains at the plasma membrane enriched in ganglioside GM1, cholesterol, and phosphatidylinositol 4,5 bisphosphate [PI[4,5]P2] Such lipid rafts correspond to membrane areas stabilized by the presence of cholesterol within a liquid-ordered phase in which lateral diffusion of proteins and lipids is limited, resulting in the clustering of specific components [20]. We have observed budding of the immunogold-labeled DBH clusters present on endosomes (unpublished data)

CONCLUSION
Proc Natl Acad Sci U
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