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.

Highlights

  • Neurons are highly polarized cells with a central cell body and multiple branched dendrite extensions and a long axon

  • These findings indicate that the dendritic endoplasmic reticulum (ER) and Golgi outposts (GOs) constitute a secretory pathway which is spatially separated from the somatic pathway but is functionally distinct from the conventional secretory pathway

  • It is clear that local protein transport machinery at remote sites away from the central cell body is important in facilitating efficient transport of nascent membrane proteins to their functional sub-domains in response to synaptic stimuli

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Summary

INTRODUCTION

Neurons are highly polarized cells with a central cell body (soma) and multiple branched dendrite extensions and a long axon. Given the importance of the Golgi apparatus in post-translational modifications and anterograde transport of newly synthesized soluble and membrane proteins, more extensive studies have been carried out on the local secretory systems of dendrites compared with axons and, this review will focus on the local secretory organelles of dendrites. These dendritic Golgi units are known as Golgi outposts (GOs) (Horton and Ehlers, 2003) Subsequent to their identification, local secretory organelles have been shown to be essential for dendritic development and maintenance in neuronal cell systems. We review the findings describing local protein trafficking pathways in dendrites, and the role of Golgi structures, obtained from different neuronal systems, point out the strengths and limitations of these models, and emphasize the emerging opportunities of using human neuron systems for elucidation of local protein secretory routes in dendrites

DENDRITIC SECRETORY ORGANELLES IN Drosophila NEURONS
ROLE OF GOLGI IN DENDRITE MORPHOGENESIS IN ZEBRAFISH
Limitation of current studies
LOCAL PROTEIN TRAFFICKING IN RODENT NEURONS
Evidence of Dendritic Protein Synthesis and Trafficking in Rodent Neurons
Synaptic Control of Protein Translation and Transport in Dendrites
MEMBRANE PROTEIN TRAFFICKING IN HUMAN NEURONS
SUMMARY AND CONCLUSION
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