Protein Kinase D regulates trafficking of dendritic membrane proteins in developing neurons

BISBAL, M; CONDE, C; DONOSO, M; BOLLATI, F; SESMA, J; QUIROGA, S; DIAZ AÑEL, A. M.; MALHOTRA, V.; MARZOLO, M.P.; CÁCERES, A.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2008 vol. 28 p. 9297 - 9308

0270-6474

In non-neuronal cells inactivation of Protein Kinase D (PKD) blocks fission of 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 RNAi 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 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 dyacylglycerol 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.