Protein Kinase D1-dependent trafficking and sorting of neurotrophin receptor TrkB

CORIA, ANDREA SOLEDAD; MASSERONI, MARÍA LUJÁN; DÍAZ AÑEL, ALBERTO MARCELO

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

After determining the participation of several proteins, such as PKD1, in an intracellular trafficking regulatory pathway, we have decided to study their role in neuronal polarity establishment, specifically through the analysis of Tropomyosin-related kinase receptors (TrkA and TrkB) trafficking and sorting. We have observed that in the absence of its specific ligand Brain Derived Neurotrophic Factor (BDNF), TrkB receptor is actively localized in the somatodendritic and axonal compartment of cultured rat hippocampal neurons. In the absence of an active PKD1, a remarkable change in the TrkB distribution was detected, with preferential localization in the primary dendrite and soma. In addition, there was a significant reduction in the length of dendrite branches, but no effect in their number was noticed. When non permeabilized neurons were analyzed, a reduction in the membrane expression of this receptor was observed when a small interference RNA for this kinase was expressed. In neurons transfected with TrkB and then treated with specific PKC and PLC inhibitors, both proteins involved in the PKD1-regulated pathway, we have also observed a remarkable reduction in dendritic length. These results confirm that PKD1 play a key role in the regulation of vesicles carrying TrkB, and that the presence of this receptor at the neuronal surface would be essential for dendrite length development.