title: Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons.
abstract: 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.
authors.affiliation: Laboratory of Neurobiology and Cell Biology, Instituto Investigacion Medica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, 5016 Córdoba, Argentina.
authors.forename: Mariano
authors.initials: M
authors.lastname: Bisbal
authors.forename: Cecilia
authors.initials: C
authors.lastname: Conde
authors.forename: Maribel
authors.initials: M
authors.lastname: Donoso
authors.forename: Flavia
authors.initials: F
authors.lastname: Bollati
authors.forename: Juliana
authors.initials: J
authors.lastname: Sesma
authors.forename: Santiago
authors.initials: S
authors.lastname: Quiroga
authors.forename: Alberto
authors.initials: A
authors.lastname: Díaz Añel
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Marzolo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cáceres
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011493:Protein Kinase C; D011494:Protein Kinases / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D014743:Videotape Recording / Q000379:methods; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008164:Luminescent Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; D011494:Protein Kinases; C089212:protein kinase D; D011493:Protein Kinase C
references.citation: Nature. 1995 Jun 15;375(6532):592-4
references.pmid: 7791876
references.citation: J Cell Biol. 2003 Sep 29;162(7):1317-28
references.pmid: 14517209
references.citation: Traffic. 2003 Apr;4(4):273-88
references.pmid: 12694565
references.citation: EMBO J. 2000 Jun 15;19(12):2935-45
references.pmid: 10856238
references.citation: Neuron. 1998 May;20(5):855-67
references.pmid: 9620691
references.citation: Nat Cell Biol. 2004 Feb;6(2):106-12
references.pmid: 14743217
references.citation: J Neurosci. 2002 Dec 15;22(24):10643-52
references.pmid: 12486157
references.citation: J Cell Biol. 2007 Dec 17;179(6):1123-31
references.pmid: 18086912
references.citation: Trends Cell Biol. 2001 Dec;11(12):483-6
references.pmid: 11719053
references.citation: J Biol Chem. 2000 Jun 16;275(24):18476-81
references.pmid: 10764790
references.citation: Annu Rev Neurosci. 1994;17:267-310
references.pmid: 8210176
references.citation: Oncogene. 2002 Mar 28;21(14):2154-60
references.pmid: 11948398
references.citation: EMBO J. 2001 Nov 1;20(21):5982-90
references.pmid: 11689438
references.citation: Nat Cell Biol. 2003 Feb;5(2):126-36
references.pmid: 12545172
references.citation: J Neurosci. 2001 Apr 1;21(7):2361-72
references.pmid: 11264310
references.citation: J Biol Chem. 1997 Jan 10;272(2):952-60
references.pmid: 8995387
references.citation: J Cell Biol. 2008 Feb 25;180(4):827-42
references.pmid: 18299352
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7051-7
references.pmid: 11416186
references.citation: Mol Cell Neurosci. 2005 Jun;29(2):173-80
references.pmid: 15911342
references.citation: Cell. 1999 Jul 9;98(1):59-68
references.pmid: 10412981
references.citation: Trends Cell Biol. 2002 Apr;12(4):193-200
references.pmid: 11978539
references.citation: J Cell Biol. 2005 Apr 11;169(1):83-91
references.pmid: 15824133
references.citation: Science. 2002 Jan 11;295(5553):325-8
references.pmid: 11729268
references.citation: J Biol Chem. 2000 Dec 22;275(51):40048-56
references.pmid: 10998417
references.citation: Curr Biol. 2004 Jan 20;14(2):88-98
references.pmid: 14738729
references.citation: Nat Neurosci. 2006 May;9(5):622-7
references.pmid: 16604070
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8870-5
references.pmid: 16735477
references.citation: Oncogene. 1999 Aug 5;18(31):4440-9
references.pmid: 10442635
references.citation: Neuron. 2000 May;26(2):281-2
references.pmid: 10839344
references.citation: J Biol Chem. 2006 Jul 7;281(27):18888-900
references.pmid: 16651260
references.citation: EMBO J. 2003 Jan 2;22(1):109-20
references.pmid: 12505989
references.citation: Neuron. 2000 May;26(2):465-72
references.pmid: 10839364
references.citation: Mol Biol Cell. 2004 Jul;15(7):3433-49
references.pmid: 15090620
references.citation: Neuron. 2003 Oct 9;40(2):277-95
references.pmid: 14556709
references.citation: FEBS Lett. 1999 Sep 3;457(3):515-21
references.pmid: 10471840
references.citation: Dev Cell. 2005 Jul;9(1):75-86
references.pmid: 15992542
references.citation: Am J Physiol Renal Physiol. 2003 Sep;285(3):F377-87
references.pmid: 12890661
references.citation: Neuron. 2003 Feb 20;37(4):611-24
references.pmid: 12597859
references.citation: EMBO J. 1999 Oct 15;18(20):5567-76
references.pmid: 10523301
references.citation: J Cell Biol. 1998 Oct 19;143(2):443-55
references.pmid: 9786954
references.citation: Nat Rev Neurosci. 2005 Mar;6(3):201-14
references.pmid: 15711600
references.citation: Cell. 2001 Feb 9;104(3):409-20
references.pmid: 11239398
references.citation: Neuron. 2005 Dec 8;48(5):757-71
references.pmid: 16337914
references.citation: J Cell Sci. 2003 Apr 1;116(Pt 7):1209-17
references.pmid: 12615964
references.citation: Cell. 2006 Oct 6;127(1):35-7
references.pmid: 17018271
references.citation: Mutat Res. 1995 Dec;333(1-2):153-60
references.pmid: 8538623
references.citation: Curr Biol. 2005 Oct 25;15(20):1820-6
references.pmid: 16243028
references.citation: Immunity. 1996 Oct;5(4):353-63
references.pmid: 8885868
references.citation: FEBS Lett. 2003 Jul 3;546(1):81-6
references.pmid: 12829240
references.citation: J Biol Chem. 2000 Jun 2;275(22):17114-21
references.pmid: 10748111
references.citation: Cell. 2006 Oct 6;127(1):113-24
references.pmid: 17018281