Regulation of Golgi outpost formation by LIMK1, PKD1, and BARS

ALFREDO CÁCERES

Montevideo

Simposio; Siymposium Development and Plasticity of the Nervous System; 2012

Instituto Clemente Estable y Universidad de la Republica

The neuronal Golgi apparatus localizes to the perinuclear region and also extends into dendrites as tubulo-vesicular structures designated as Golgi outposts (GOps). Interestingly, NMDAR are sorted at the ER from AMPAR, bypassing the somatic Golgi and merging instead from GOps, raising the possibility that may serve as platforms for local delivery of synaptic receptors. Disruption of the dynein/dynactin complex reduces the number of GOps and dendritic branches, suggesting a direct relationship between their abundance and dendritic complexity. However, the crucial question of how GOps are generated remains unanswered. Two possible scenarios have been proposed, one involving fragmentation of the somatic Golgi followed by transport into dendrites and other one involving local de novo production from dendritic ER. Live cell imaging of cultured hippocampal neurons reveals that GOps are generated from the somatic Golgi by a sequence of events involving: 1) Tubulation of a Golgi cisterna; 2) Elongation and penetration into a dendrite (deployment); 3) Tubule fission; and 4) Condensation of the fissioned tubule. Suppression of LIMK1, PKD1 or BARs reduce the number of GOps and induce Golgi deployment/tubulation without fission; by contrast, ectopic expression of these proteins or LPA treatment or reelin stimulate Golgi outpost formation, an effect dependent on RhoA-ROCK and dynamin.