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The Journal of Neuroscience, September 10, 2008, 28(37):9297-9308; doi:10.1523/JNEUROSCI.1879-08.2008

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Cellular/Molecular
Protein Kinase D Regulates Trafficking of Dendritic Membrane Proteins in Developing Neurons

Mariano Bisbal,¹ Cecilia Conde,¹ Maribel Donoso,² Flavia Bollati,¹ Juliana Sesma,¹ Santiago Quiroga,³ Alberto Díaz Añel,¹ Vivek Malhotra,⁴ Maria Paz Marzolo,² and Alfredo Cáceres¹

¹Laboratory of Neurobiology and Cell Biology, Instituto Investigacion Medica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 5016 Córdoba, Argentina, ²Centro de Regulación Celular y Patología, Departamento Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile, ³Centro de Investigaciones en Química Biológica de Córdoba-CONICET, 5000 Córdoba, Argentina, and ⁴Department of Biology, University of California, San Diego, La Jolla, California 92093

Correspondence should be addressed to Alfredo Cáceres, Instituto Investigacion Medica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, Avenida Friuli 2434, 5016 Córdoba, Argentina. Email: acaceres{at}immf.uncor.edu

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.

Key words: PKD1; Golgi apparatus; vesicles; sorting; dendritic membrane proteins; neurons

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Received April 29, 2008; revised July 19, 2008; accepted Aug. 3, 2008.

Correspondence should be addressed to Alfredo Cáceres, Instituto Investigacion Medica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, Avenida Friuli 2434, 5016 Córdoba, Argentina. Email: acaceres{at}immf.uncor.edu

This article has been cited by other articles:

				S. Dupraz, D. Grassi, M. E. Bernis, L. Sosa, M. Bisbal, L. Gastaldi, I. Jausoro, A. Caceres, K. H. Pfenninger, and S. Quiroga The TC10-Exo70 Complex Is Essential for Membrane Expansion and Axonal Specification in Developing Neurons J. Neurosci., October 21, 2009; 29(42): 13292 - 13301. [Abstract] [Full Text] [PDF]

				K. Czondor, K. Ellwanger, Y. F. Fuchs, S. Lutz, M. Gulyas, I. M. Mansuy, A. Hausser, K. Pfizenmaier, and K. Schlett Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons Mol. Biol. Cell, April 1, 2009; 20(7): 2108 - 2120. [Abstract] [Full Text] [PDF]

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