PKD1 regulation of Trk receptors? trafficking: effect on neuronal development and functionality

CORIA, ANDREA SOLEDAD; MEAKIN, SUSAN; DIAZ AÑEL, A. M.

Córdoba

Congreso; LII Reunión Anual de SAIB; 2016

SAIB

Previous works in polarized cells, such as neurons, have shown the main role of PKD1 in protein sorting, where blocking of this kinase activity was able to change normal dendritic markers? localization, directing them to the axon terminal, and showing at the same time a delay in dendritic growing.In this work, we analyzed how blocking of the PLC-PKC-PKD1 pathway would affect the transport of two neurotrophin receptors, TrkA/TrkB, and if it could also have an effect in their activity.Our work have shown that in neurons, blocking of this pathway led to retention of TrkA at the Golgi apparatus, similar as the effect described for membrane proteins in non-polarized HeLa cells. Moreover, when the pathway was inhibited, TrkB changed from a somatodendritic position to an apical dendrite localization. Additionally, sorting changes of these receptors have led to defects in their specific ligand response, and in the case of TrkB, it affected processes such as LTP and status epilepticus.Our results have revealed the complexity of trafficking regulation in polarized cells. At least in neurons, PKD1-dependent pathway would be participating not only in membrane fission regulation, but also in protein sorting to different compartments, such as axons, basal and apical dendrites. It is clear that PKD1 role in trafficking depends both on the type of transported protein and on its final destination.