PT  - JOURNAL ARTICLE
AU  - Mariano Bisbal
AU  - Cecilia Conde
AU  - Maribel Donoso
AU  - Flavia Bollati
AU  - Juliana Sesma
AU  - Santiago Quiroga
AU  - Alberto Díaz Añel
AU  - Vivek Malhotra
AU  - Maria Paz Marzolo
AU  - Alfredo Cáceres
TI  - Protein Kinase D Regulates Trafficking of Dendritic Membrane Proteins in Developing Neurons
AID  - 10.1523/JNEUROSCI.1879-08.2008
DP  - 2008 Sep 10
TA  - The Journal of Neuroscience
PG  - 9297--9308
VI  - 28
IP  - 37
4099  - http://www.jneurosci.org/content/28/37/9297.short
4100  - http://www.jneurosci.org/content/28/37/9297.full
SO  - J. Neurosci.2008 Sep 10; 28
AB  - In non-neuronal cells, inactivation of protein kinase D (PKD) blocks fission of trans-Golgi network (TGN) transport carriers, inducing the appearance of long tubules filled with cargo. We now report on the function of PKD1 in neuronal protein trafficking. In cultured hippocampal pyramidal cells, the transferrin receptor (TfR) and the low-density receptor-related protein (LRP) are predominantly transported to dendrites and excluded from axons. Expression of kinase-inactive PKD1 or its depletion by RNA interference treatment dramatically and selectively alter the intracellular trafficking and membrane delivery of TfR- and LRP-containing vesicles, without inhibiting exit from the TGN or inducing Golgi tubulation. After PKD1 suppression, dendritic membrane proteins are mispackaged into carriers that transport VAMP2; these vesicles are distributed to both axons and dendrites, but are rapidly endocytosed from dendrites and preferentially delivered to the axonal membrane. A kinase-defective mutant of PKD1 lacking the ability to bind diacylglycerol and hence its Golgi localization does not cause missorting of TfR or LRP. These results suggest that in neurons PKD1 regulates TGN-derived sorting of dendritic proteins and hence has a role in neuronal polarity.