ABSTRACT
Secretory granules (SGs) are specialized organelles responsible for the storage and regulated release of various biologically active molecules from the endocrine and exocrine systems. Thus, proper SG biogenesis is critical to normal animal physiology. Biogenesis of SGs starts at the trans-Golgi network (TGN), where immature SGs (iSGs) bud off and undergo maturation before fusing with the plasma membrane (PM). How iSGs mature is unclear, but emerging studies have suggested an important role for the endocytic pathway. The requirement for endocytic machinery in SG maturation blurs the line between SGs and another class of secretory organelles called lysosome-related organelles (LROs). Therefore, it is important to re-evaluate the differences and similarities between SGs and LROs.
Subject(s)
Cell Membrane/metabolism , Endocytosis/physiology , Endoplasmic Reticulum/metabolism , Exocytosis/physiology , Secretory Vesicles/metabolism , trans-Golgi Network/metabolism , Animals , Biological Transport , Cell Membrane/ultrastructure , Endoplasmic Reticulum/ultrastructure , Eukaryotic Cells/metabolism , Eukaryotic Cells/ultrastructure , Humans , Lysosomes/metabolism , Lysosomes/ultrastructure , Organelle Biogenesis , Secretory Vesicles/ultrastructure , Signal Transduction , trans-Golgi Network/ultrastructureABSTRACT
Secretory granules (SGs) are organelles responsible for regulated exocytosis of biologically active molecules in professional secretory cells. Maturation of SGs is a crucial process in which cargoes of SGs are processed and activated, allowing them to exert their function upon secretion. Nonetheless, the intracellular trafficking pathways required for SG maturation are not well defined. We recently performed an RNA interference (RNAi) screen in Drosophila larval salivary glands to identify trafficking components needed for SG maturation. From the screen, we identified several Rab GTPases (Rabs) that affect SG maturation. Expression of constitutively active (CA) and dominant-negative (DN) forms narrowed down the Rabs important for this process to Rab5, Rab9 and Rab11. However, none of these Rabs localizes to the limiting membrane of SGs. In contrast, examination of endogenously YFP-tagged Rabs (YRabs) in larval salivary glands revealed that YRab1 and YRab6 localize to the limiting membrane of immature SGs (iSGs) and SGs. These findings provide new insights into how Rab GTPases contribute to the process of SG maturation.
