Secretory outposts for the local processing of membrane cargo in neuronal dendrites

Abstract

The large size and geometric complexity of neuronal dendrites necessitate specialized mechanisms to both deliver postsynaptic cargo over extended distances and regulate dendritic composition on a submicron scale. Despite the fundamental importance of membrane trafficking in dendrite growth, synapse formation and plasticity, the organelles and cellular rules governing postsynaptic trafficking are only now emerging. Here we review what is currently known about dendritic secretory organelles and their role in the development, maintenance and plasticity of postsynaptic compartments.

Figure 1. Spatial organization of the Golgi apparatus in hippocampal neurons

A. Immunolabeling of the somatodendritic marker MAP2 (red) and the cis-Golgi matrix protein GM130 (green) in a cultured hippocampal neuron. Scale bar, 10 μm. Inset: higher magnification of GM130 labeling illustrating Golgi outposts dispersed in the apical dendrite (arrowheads). Other dendrites lack GM130 positive Golgi outposts (arrows). B. Immunogold labeling for GM130 (arrows) demonstrating the presence of isolated Golgi stacks in the apical dendrite of a pyramidal neuron in vivo. Scale bar, 1 μm. Inset: higher magnification. A and B adapted from (24); reprinted with permission from Elsevier, copyright 2005. C. α-mannosidase II (C1) and giantin (C2) immunogold labeling (red arrowheads) in dendritic spines of CA1 pyramidal neurons in vivo. T, presynaptic terminal; S, spine; D, dendrite Scale bar, 250 nm. Adapted from (9); reprinted with permission from Elsevier, copyright 2001.

Figure 2. ER-to-Golgi trafficking in neuronal dendrites

A. VSVG-ts-YFP (red) distribution in a hippocampal neuron dendrite expressing a CFP-tagged Golgi marker (GalT-CFP), before (ER), and 20 min after (post-ER) release of temperature-dependent ER exit blockade (39.5°C to 32°C switch, see text), illustrating the accumulation of post-ER cargo in dendritic Golgi outposts (arrows). Adapted from (11); reprinted with permission from the Society for Neuroscience, copyright 2003. B. VSVG-ts-GFP (green) after a 20°C TGN-exit blockade (see text) in hippocampal neurons expressing a red cell-fill, showing the presence of secretory platforms at primary (1°), secondary (2°), and tertiary (3°) dendritic branch points. C. Electron micrograph of GM130 immunogold labeling (arrows) marking a Golgi outpost located at a dendritic branch point in vivo. B and C adapted from (24); reprinted with permission from Elsevier, copyright 2005. D. Model for dual ER-to-Golgi trafficking in dendrites. While ER and ER exit sites (ERES) are distributed throughout the somatodendritic compartment, only a subset of dendrites contain Golgi outposts. Consequently, dendritic post-ER carriers are transported long distances to the somatic Golgi in dendrites lacking Golgi outposts (I). In dendrites containing Golgi outposts, post-ER carriers either bypass dendritic outposts (I) or deliver their cargo to outposts for local processing (II).

Figure 3. The dendritic ER and the spine apparatus

A. Three-dimensional reconstruction of serial electron micrographs showing the distribution of smooth ER (SER, dark grey) in a short segment of a CA1 hippocampal neuron dendrite in vivo. Large flat compartments (arrowheads) are linked by thin extensions (thin arrows). Note the extension of SER membranes within the head of a mature spine (crossed arrow). Adapted from (68); reprinted with permission from the Society for Neuroscience, copyright 2002. B. Electron micrograph of the spine apparatus (SA) showing the lamination of cisternae (thick arrows) between regions of high electron density (wavy arrows). Adapted from (4); reprinted with permission from the Society for Neuroscience, copyright 1997. Scale bar, 0.5 μm. C. Schematic representation of a large dendritic spine illustrating vesicles at the tip of the SA, the presence of glutamate receptors in the SA, and the presence of ribosomes (r) and polysomes (p) at the base of the spine.

Figure 4. Polarized secretory trafficking and asymmetric dendritic growth in hippocampal pyramidal neurons

A. Polarization of the somatic Golgi in pyramidal neurons (left) versus GABAergic inhibitory interneurons (right). Shown is a pseudocolored map of GM130 fluorescence intensity (Golgi-IR) as a function of radial orientation relative to the axis formed by the longest dendrite (0°, up). Insets: fluorescence fractions in each quadrant. Note that the somatic Golgi is polarized towards the apical dendrite in neurons displaying polarized dendritic trees. B. Polarization of the somatic Golgi (red) correlates with asymmetric dendrite growth to produce a single apical dendrite (1), imposing a bias to post-Golgi trafficking (blue arrows). Alteration of pre- and post-Golgi trafficking either by overexpressing dominant negative (dn) mutants of PKD or Arf1, by Sar1 RNAi knockdown, or using BFA prevents dendritic growth (1)(2). Axons are not affected under these conditions (not illustrated). Dispersion of the somatic Golgi by overexpression of GRASP65 abolishes the asymmetric growth of the apical dendrite without affecting total dendritic growth (3). Adapted from (24); reprinted with permission from Elsevier, copyright 2005.