Role of Protein Kinase D1 in Group I metabotropic glutamate receptors trafficking

MASSERONI, MARÍA LUJÁN; GASTALDI, LAURA; JAUSORO, IGNACIO; QUASSOLLO, GONZALO; CORIA, ANDREA SOLEDAD; 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)

Most of neuronal dendritic and axonal membrane protein sorting, a key process for establishment and maintenance of neuron polarity, occurs at the Trans-Golgi Network (TGN). Metabotropic glutamate receptors belong to G protein-coupled receptor (GPCR) family of seven-transmembrane domain; they contribute to synaptic plasticity, hence in learning and memory processes. Their transport towards their final localization - dendrites or axons - is still a complex and not well-characterized process. Protein Kinase D1 (PKD1) is a major component in membrane trafficking events; in neurons, PKD1 participates in dendritic membrane proteins sorting, such as transferrin receptor (TfR). These previous observations lead us to hypothesize that PKD1 regulates Group I metabotropic glutamate receptors (mGluR) sorting, since they are dendritic membrane proteins. Using 14 DIV hippocampal neurons, we evaluate the effect in the mGluR1 and mGluR5 intracellular trafficking from the TGN to proper dendritic domain by using: i) depletion of the PKD1 by short harpin RNA, ii) a dominant negative mutant (PKD1 kinase dead), and iii) chemical inhibitors. Taking together, the results showed that the two receptors are missorted and inserted in both dendritic and axonal membranes. Moreover, we proved that the signaling pathway whereby PKD1 is activated in neurons was through Phospholipase C (PLC) and Protein kinase C (PKC).