Polarized Secretory Trafficking Directs Cargo for Asymmetric Dendrite Growth and Morphogenesis

Abstract

Proper growth of dendrites is critical to the formation of neuronal circuits, but the cellular machinery that directs the addition of membrane components to generate dendritic architecture remains obscure. Here, we demonstrate that post-Golgi membrane trafficking is polarized toward longer dendrites of hippocampal pyramidal neurons in vitro and toward apical dendrites in vivo. Small Golgi outposts partition selectively into longer dendrites and are excluded from axons. In dendrites, Golgi outposts concentrate at branchpoints where they engage in post-Golgi trafficking. Within the cell body, the Golgi apparatus orients toward the longest dendrite, and this Golgi polarity precedes asymmetric dendrite growth. Manipulations that selectively block post-Golgi trafficking halt dendrite growth in developing neurons and cause a shrinkage of dendrites in mature pyramidal neurons. Further, disruption of Golgi polarity produces neurons with symmetric dendritic arbors lacking a single longest principal dendrite. These results define a novel polarized organization of neuronal secretory trafficking and demonstrate a mechanistic link between directed membrane trafficking and asymmetric dendrite growth.

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

“…A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al, 2000;Fujita and Okamoto, 2005;Horton et al, 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al, 1999;Pierce et al, 2001;Sytnyk et al, 2002;Horton and Ehlers, 2003).…”

“…In axonal outgrowth and extension, an increasing amount of data suggests that membrane supply and targeting of proteins are regulated in a different way compared with dendritic elongation (Silverman et al, 2001; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -09 -0957) on February 11, 2009. Horton et al, 2005;Lein et al, 2007;Takemoto-Kimura et al, 2007;Ye et al, 2007).…”

“…PKD activity has been recently implicated in regulating early neuronal polarization (Yin et al, 2008), early dendritic development (Horton et al, 2005), or selective transport and endocytosis of dendritic proteins (Bisbal et al, 2008). In the present work, we have used a newly developed reporter of PKD activity and studied transgenic mice with neuron-specific, inducible expression of a dominant-negative-acting PKD1 mutant to unravel the role of PKD in mature hippocampal neurons, both in vitro and in vivo.…”

“…The dispersed localization of the Golgi apparatus indicates unique spatial regulation of the neuronal secretory pathway compared with other mammalian cells. Recent investigations on hippocampal pyramidal cells indicated that Golgi outposts located in the dendritic shafts (Sytnyk et al, 2002;Horton and Ehlers, 2003) and the perinuclear Golgi apparatus oriented toward the longest dendrite (Horton et al, 2005) can provide the necessary membrane supply for intensive dendritic growth. In axonal outgrowth and extension, an increasing amount of data suggests that membrane supply and targeting of proteins are regulated in a different way compared with dendritic elongation (Silverman et al, 2001; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -09 -0957) on February 11, 2009.…”

“…© 2009 by The American Society for Cell Biology Horton et al, 2005;Lein et al, 2007;Takemoto-Kimura et al, 2007;Ye et al, 2007). Based on studies in nonneuronal cells, protein kinase D (PKD) is known to play a key regulatory role in secretory pathways.…”