Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons.
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.
Bisbal
Mariano
M
Laboratory of Neurobiology and Cell Biology, Instituto Investigacion Medica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, 5016 Córdoba, Argentina.
Conde
Cecilia
C
Donoso
Maribel
M
Bollati
Flavia
F
Sesma
Juliana
J
Quiroga
Santiago
S
Díaz Añel
Alberto
A
Malhotra
Vivek
V
Marzolo
Maria Paz
MP
Cáceres
Alfredo
A
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
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
Nature. 1995 Jun 15;375(6532):592-4
7791876
J Cell Biol. 2003 Sep 29;162(7):1317-28
14517209
Traffic. 2003 Apr;4(4):273-88
12694565
EMBO J. 2000 Jun 15;19(12):2935-45
10856238
Neuron. 1998 May;20(5):855-67
9620691
Nat Cell Biol. 2004 Feb;6(2):106-12
14743217
J Neurosci. 2002 Dec 15;22(24):10643-52
12486157
J Cell Biol. 2007 Dec 17;179(6):1123-31
18086912
Trends Cell Biol. 2001 Dec;11(12):483-6
11719053
J Biol Chem. 2000 Jun 16;275(24):18476-81
10764790
Annu Rev Neurosci. 1994;17:267-310
8210176
Oncogene. 2002 Mar 28;21(14):2154-60
11948398
EMBO J. 2001 Nov 1;20(21):5982-90
11689438
Nat Cell Biol. 2003 Feb;5(2):126-36
12545172
J Neurosci. 2001 Apr 1;21(7):2361-72
11264310
J Biol Chem. 1997 Jan 10;272(2):952-60
8995387
J Cell Biol. 2008 Feb 25;180(4):827-42
18299352
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7051-7
11416186
Mol Cell Neurosci. 2005 Jun;29(2):173-80
15911342
Cell. 1999 Jul 9;98(1):59-68
10412981
Trends Cell Biol. 2002 Apr;12(4):193-200
11978539
J Cell Biol. 2005 Apr 11;169(1):83-91
15824133
Science. 2002 Jan 11;295(5553):325-8
11729268
J Biol Chem. 2000 Dec 22;275(51):40048-56
10998417
Curr Biol. 2004 Jan 20;14(2):88-98
14738729
Nat Neurosci. 2006 May;9(5):622-7
16604070
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8870-5
16735477
Oncogene. 1999 Aug 5;18(31):4440-9
10442635
Neuron. 2000 May;26(2):281-2
10839344
J Biol Chem. 2006 Jul 7;281(27):18888-900
16651260
EMBO J. 2003 Jan 2;22(1):109-20
12505989
Neuron. 2000 May;26(2):465-72
10839364
Mol Biol Cell. 2004 Jul;15(7):3433-49
15090620
Neuron. 2003 Oct 9;40(2):277-95
14556709
FEBS Lett. 1999 Sep 3;457(3):515-21
10471840
Dev Cell. 2005 Jul;9(1):75-86
15992542
Am J Physiol Renal Physiol. 2003 Sep;285(3):F377-87
12890661
Neuron. 2003 Feb 20;37(4):611-24
12597859
EMBO J. 1999 Oct 15;18(20):5567-76
10523301
J Cell Biol. 1998 Oct 19;143(2):443-55
9786954
Nat Rev Neurosci. 2005 Mar;6(3):201-14
15711600
Cell. 2001 Feb 9;104(3):409-20
11239398
Neuron. 2005 Dec 8;48(5):757-71
16337914
J Cell Sci. 2003 Apr 1;116(Pt 7):1209-17
12615964
Cell. 2006 Oct 6;127(1):35-7
17018271
Mutat Res. 1995 Dec;333(1-2):153-60
8538623
Curr Biol. 2005 Oct 25;15(20):1820-6
16243028
Immunity. 1996 Oct;5(4):353-63
8885868
FEBS Lett. 2003 Jul 3;546(1):81-6
12829240
J Biol Chem. 2000 Jun 2;275(22):17114-21
10748111
Cell. 2006 Oct 6;127(1):113-24
17018281