Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models

Abstract

A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmission between neurons. Intracellular membrane trafficking is paramount to establish and maintain neuronal structure; perturbation in trafficking results in defects in neurodevelopment and neurological disorders. Given the physical distance from the cell body to the distal sites of the axon and dendrites, transport of newly synthesized membrane proteins from the central cell body to their functional destination at remote, distal sites represents a conundrum. With the identification of secretory organelles in dendrites, including endoplasmic reticulum (ER) and Golgi outposts (GOs), recent studies have proposed local protein synthesis and trafficking distinct from the conventional anterograde transport pathways of the cell body. A variety of different model organisms, including Drosophila, zebrafish, and rodents, have been used to probe the organization and function of the local neuronal secretory network. Here, we review the evidence for local secretory trafficking pathways in dendrites in a variety of cell-based neuronal systems and discuss both the similarities and differences in the organization and role of the local secretory organelles, especially the GOs. In addition, we identify the gaps in the current knowledge and the potential advances using human induced pluripotent stem cells (iPSCs) in defining local membrane protein trafficking in human neurons and in understanding the molecular basis of neurological diseases.

The intracellular and plasma membrane pools of PI4P control megakaryocyte maturation and proplatelet formation

“…MKs are not the only cells in which Golgi fragmentation has been observed. Small Golgi fragments have been found in neuronal dendrites that are separated from the perinuclear Golgi and serve as secretory organelles 31 . These neuronal Golgi fragments are called Golgi outposts (GOs) 32 .…”

“…These neuronal Golgi fragments are called Golgi outposts (GOs) 32 . It has been shown that GOs are important for dendrite growth and branching because GOs ablation reduces dendritic extension and retraction 33 and they can also interact with cytoskeletal remodelling and motor proteins 31 . Since GOs in neurons are important for dendrite growth, the Golgi fragments in MKs may have a similar role in the growth of the DMS and proplatelets.…”

Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi?

“…In addition, APP processing and Aβ production was detected in the axonal compartment in transgenic mice 43 and local processing of APP detected in the dendrites was observed after APP overexpression 34,44 . Interestingly, small Golgi units, called Golgi outposts (GOs), which include the TGN compartment, are scattered throughout the dendrites and function as a component of a local secretory network 45 and may potentiate APP processing.…”

“…There is evidence of local secretory pathways in dendrites and also possibly axons, distant from the cell body of the neuron. A specialised set of Golgi ministacks known as GOs are located in dendrites, which are independent from the somatic Golgi 45,109 . However, it is unknown if APP and the secretases are synthesised locally in the dendrites and/or transported from the soma ER to the GOs.…”

Nanoscale Sub-Compartmentalization of the Dendritic Spine Compartment

“…As the spine neck diameter diminishes, it is energetically and mechanically more costly to transport endosomal vesicles from the ER outposts in the dendrite to the PSD through the spine actin meshwork [ 207 ]. Dendritic ER and Golgi outposts are well documented in rodent hippocampal neurons, particularly at dendritic branching points [ 208 ] and high-pressure freezing fixation (without chemical fixation) combined with transmission electron microscopy has revealed smooth ER and Golgi outposts inside dendritic spines [ 209 ] ( Figure 4 ).…”