Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells

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Abstract

Secretory granule formation requires selection of soluble and membrane proteins into nascent secretory granules, and exclusion of proteins not required for the function of secretory granules. Both selection and exclusion presumably can occur in the compartment where assembly of the secretory granule begins, the trans most cisternae of the Golgi complex. Current research focused on the initial stages of secretory granule formation includes a search for the ‘signals’ which may mediate active sorting of components into secretory granules, and the role of aggregation of regulated secretory proteins in sorting. In addition, the temporal sequence of the sorting events in the Golgi, and post-Golgi compartments has gained much attention, as summarized by the alternative but not mutually exclusive ‘sorting for entry’ vs. ‘sorting by retention’ models. ‘Sorting for entry’ which encompasses the most popular models requires selection of cargo and membrane and exclusion of non-secretory granule proteins in the TGN prior to secretory granule formation. ‘Sorting by retention’ stipulates that protein selection or exclusion may occur after secretory granule formation: secretory granule specific components are retained during maturation of the granule while non-secretory granule molecules are removed in vesicles which bud from maturing secretory granules. Finally, some progress has been made in the identification of cytosolic components involved in the budding of nascent secretory granules from the TGN. This review will focus on the recent data concerning the events in secretory granule formation which occur, in the trans-Golgi network.

Keywords

Secretion
Regulated secretion
trans-Golgi network
Vesicle formation
Immature secretory granule

Abbreviations

TGN, trans-Golgi network
ISG, immature secretory granule
MSG, mature secretory granule
CSV, constitutive secretory vesicle
CCV, clathrin-coated vesicle
CgB, chromogranin B
SgII, secretogranin II
hsPG, heparan sulphate proteoglycan
PCs, prohormone converting enzymes
LDCV, large dense core vesicles
DTT, dithiothreitol
ARF, ADP-ribosylation factor
AP-1, adaptor protein-1
PLD, phospholipase D
GH, growth hormone
PRL, prolactin
MPR, mannose-6-phosphate receptor
PIP2 (phosphatidylinositol 4,5-bisphosphate)
PITP, phosphatidylinositol transfer protein
PI, phosphatidylinositol

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