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.; MALHOTRA, V.; MARZOLO, M.P.; CÁCERES, A.

JOURNAL OF NEUROSCIENCE

Society for Neuroscience

Lugar: Washington DC; Año: 2008 p. 9297 - 9308

0270-6474

In non-neuronal cells, inactivation of protein kinaseD(PKD) blocks fission of trans-Golgi network (TGN) transport carriers, inducing theappearance of long tubules filled with cargo. We now report on the function of PKD1 in neuronal protein trafficking. In culturedhippocampal pyramidal cells, the transferrin receptor (TfR) and the low-density receptor-related protein (LRP) are predominantlytransported to dendrites and excluded from axons. Expression of kinase-inactive PKD1 or its depletion by RNA interference treatmentdramatically and selectively alter the intracellular trafficking and membrane delivery of TfR- and LRP-containing vesicles, withoutinhibiting exit from the TGN or inducing Golgi tubulation. After PKD1 suppression, dendritic membrane proteins are mispackaged intocarriers that transport VAMP2; these vesicles are distributed to both axons and dendrites, but are rapidly endocytosed from dendritesand preferentially delivered to the axonal membrane. A kinase-defective mutant of PKD1 lacking the ability to bind diacylglycerol andhence its Golgi localization does not cause missorting of TfR or LRP. These results suggest that in neurons PKD1 regulates TGN-derivedsorting of dendritic proteins and hence has a role in neuronal polarity.Key words: PKD1; Golgi apparatus; vesicles; sorting; dendritic membrane proteins; neurons