Regulation of Golgi outpost formation

ALFREDO CÁCERES

Montevideo

Workshop; Neurosur 2012 Biomedical Neuroscience Institute and Pasteur Institute Montevideo Joint Meeting; 2012

Biomedical Neuroscience Institute (Chile) and Pasteur Institute Montevideo

Neurons are highly polarized cells with molecularly and functionally distinct domains, such as axons, dendrites, synapses, axon initial segment (AIS) and Ranvier nodes. From the first steps of neurite outgrowth to maturity, the total membrane surface area of neurons increase by several orders of magnitude, requiring massive amounts of membrane synthesis and mobilization to growing axons and dendrites, events tightly coupled with cytoskeletal assembly and dynamics at sites of active growth. Disruption of the endoplasmic reticulum (ER)-Golgi secretory pathway alters axon-dendritic formation illustrating the crucial role for membrane carrier assembly, fission, exit, delivery and addition during polarization. However, the precise mechanisms involved in the assembly and release of vesicular and tubular carriers from the Trans-Golgi Network (TGN) remain poorly understood, particularly so in neurons. Furthermore, neurons exhibit characteristic Golgi-outposts, mini-Golgi structures located within dendrites, which may contribute an additional level for regulating exocytic traffic. Using a combination of molecular biology approaches, high-resolution video microscopy and protocols to synchronize biosynthetic trafficking we have now obtained evidence suggesting that LIMK1, Protein Kinase D1, and Brefeldin A-Rybosilated Substrate (BARS) have a crucial role in regulating exit from the TGN of several axonal and dendritic membrane proteins, as well as the formation of Golgi outposts.