Morpho-functional architecture of the Golgi complex of neuroendocrine cells

Abstract

In neuroendocrine cells, prohormones move from the endoplasmic reticulum to the Golgi complex (GC), where they are sorted and packed into secretory granules. The GC is considered the central station of the secretory pathway of proteins and lipids en route to their final destination. In most mammalian cells, it is formed by several stacks of cisternae connected by tubules, forming a continuous ribbon. This organelle shows an extraordinary structural and functional complexity, which is exacerbated by the fact that its architecture is cell type specific and also tuned by the functional status of the cell. It is, indeed, one the most beautiful cellular organelles and, for that reason, perhaps the most extensively photographed by electron microscopists. In recent decades, an exhaustive dissection of the molecular machinery involved in membrane traffic and other Golgi functions has been carried out. Concomitantly, detailed morphological studies have been performed, including 3D analysis by electron tomography, and the precise location of key proteins has been identified by immunoelectron microscopy. Despite all this effort, some basic aspects of Golgi functioning remain unsolved. For instance, the mode of intra-Golgi transport is not known, and two opposing theories (vesicular transport and cisternal maturation models) have polarized the field for many years. Neither of these theories explains all the experimental data so that new theories and combinations thereof have recently been proposed. Moreover, the specific role of the small vesicles and tubules which surround the stacks needs to be clarified. In this review, we summarize our current knowledge of the Golgi architecture in relation with its function and the mechanisms of intra-Golgi transport. Within the same framework, the characteristics of the GC of neuroendocrine cells are analyzed.

Keywords: golgi complex; intra-golgi transport; morphology; neuroendocrine cells; transport vesicles; tubules.

Figure 1

Golgi structure and transport carriers in secretory cells. The Golgi ribbon is formed by adjacent Golgi stacks (Gs) separated by non-compact regions (Nc) containing tubules and vesicles. Golgi stacks are connected to the cis and trans Golgi networks (CGN and TGN). Newly synthesized cargo leaves the endoplasmic reticulum (ER) by COPII-coated vesicles (black). COPI-coated (red) vesicles mediate recycling from the Golgi and the ERGIC. Transport carriers at the TGN include clathrin-coated vesicles (blue), regulated secretory granules (Sg), and the poorly understood constitutive secretory carriers (orange) Clathrin and COPI coats are also associated to secretory granules. Heterotypic and homotypic tubular connections between cisternae may be involved in anterograde and/or retrograde intra-Golgi transport.

Figure 2

Structure of the Golgi ribbon. Electron micrographs of Epon-embedded PC12 cells. (A) The Golgi stacks (Gs) are surrounded by tubule-vesicular elements (asterisks). Arrowheads point to the non-compact area of the ribbon which connects the stacks laterally. (B) The cis and trans sides of the stacks are identified by the presence of ER exit sites (arrowhead) and secretory granules (Sg), respectively. Gs, Golgi stack; L, Lysosome; N, Nucleus. Bars, 200 nm.

Figure 3

Coated vesicles and buds. Electron micrographs of cryosections of PC12 cells. Using this methodology, membranes appear negatively stained, whereas coats are identified as electron dense areas around vesicles and buds. (A) COP- (arrows) and clathrin-coated (arrowhead) vesicles are observed in the lateral and trans Golgi sides, respectively. Note the different thickness of these coats. (B) COPII-coated bud associated to the endoplasmic reticulum (arrowhead). (C) COPI-coated bud in the lateral rim of cisterna (arrowhead). COPII- and COPI-coated buds are identified by their locations because the thickness of these coats is identical. Bar, 200 nm.