A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors.
The development of neuronal circuits is controlled by guidance molecules that are hypothesized to interact with the cholesterol-enriched domains of the plasma membrane termed lipid rafts. Whether such domains enable local intracellular signalling at the submicrometre scale in developing neurons and are required for shaping the nervous system connectivity in vivo remains controversial. Here, we report a role for lipid rafts in generating domains of local cAMP signalling in axonal growth cones downstream of ephrin-A repulsive guidance cues. Ephrin-A-dependent retraction of retinal ganglion cell axons involves cAMP signalling restricted to the vicinity of lipid rafts and is independent of cAMP modulation outside of this microdomain. cAMP modulation near lipid rafts controls the pruning of ectopic axonal branches of retinal ganglion cells in vivo, a process requiring intact ephrin-A signalling. Together, our findings indicate that lipid rafts structure the subcellular organization of intracellular cAMP signalling shaping axonal arbors during the nervous system development.
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Stefania
S
Averaimo
Sorbonne Universités, UPMC University Paris 06, UMR_S 839, Paris F-75005, France.|INSERM UMR_S 839, Paris F-75005, France.|Institut du Fer à Moulin, Paris F-75005, France.
Ahlem
A
Assali
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Oriol
O
Ros
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Sandrine
S
Couvet
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Yvrick
Y
Zagar
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Ioana
I
Genescu
Sorbonne Universités, UPMC University Paris 06, UMR_S 839, Paris F-75005, France.|INSERM UMR_S 839, Paris F-75005, France.|Institut du Fer à Moulin, Paris F-75005, France.
Alexandra
A
Rebsam
Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France.|CNRS, UMR_7210, Paris F-75012, France.|INSERM, UMR_S 968, Paris F-75012, France.
Xavier
0000-0002-0310-8047
X
Nicol
D000818:Animals; D001369:Axons / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D036382:Ephrin-A1 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D015398:Signal Transduction
D036382:Ephrin-A1; D000242:Cyclic AMP
BMC Dev Biol. 2007 Sep 17;7:103
17875204
Cell Rep. 2014 Nov 20;9(4):1191-201
25456121
J Neurosci. 2008 Apr 9;28(15):3920-4
18400890
Biochim Biophys Acta. 2011 Mar;1812(3):415-22
21147218
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20452-7
19920176
J Neurosci. 2006 Jan 18;26(3):862-72
16421306
Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5720-4
1378615
Circ Res. 2004 Jul 9;95(1):67-75
15178638
Curr Med Chem. 2013;20(1):4-21
23150999
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13776-81
21795610
Eur J Neurosci. 2014 Jun;39(11):1742-51
24628976
J Cell Biol. 2012 Aug 20;198(4):607-21
22908311
J Biol Chem. 2011 Sep 23;286(38):32962-75
21771783
Semin Cell Dev Biol. 2012 Apr;23(2):181-90
21930230
J Neurosci. 2009 Nov 4;29(44):13981-91
19890008
Biochem J. 2004 Mar 1;378(Pt 2):281-92
14662007
Annu Rev Neurosci. 2005;28:127-56
16022592
Front Cell Neurosci. 2014 Nov 13;8:376
25431549
J Cell Sci. 2005 Apr 15;118(Pt 8):1687-92
15811950
Sci STKE. 2004 Apr 28;2004(231):pe19
15126677
Nat Methods. 2007 Jan;4(1):39-42
17128267
J Neurosci. 2009 Dec 9;29(49):15434-44
20007468
PLoS One. 2009 Nov 03;4(11):e7649
19888343
Brain Struct Funct. 2016 Jan;221(1):535-61
25403254
J Comp Neurol. 2012 May 1;520(7):1562-83
22102330
Neuron. 1998 Feb;20(2):235-43
9491985
Nature. 2011 May 15;474(7351):403-6
21572435
J Vis Exp. 2009 Sep 24;(31):null
19779401
J Biol Chem. 2011 Jan 14;286(2):1181-8
21030594
Physiol Rev. 2007 Jul;87(3):965-1010
17615394
FASEB J. 2003 Jan;17(1):82-4
12475901
Neuron. 1997 Dec;19(6):1225-35
9427246
Elife. 2015 Oct 29;4:e09545
26512888
J Neurosci. 2010 Apr 28;30(17):6143-51
20427672
J Neurosci. 2004 Jul 14;24(28):6248-57
15254079
Neuron. 2004 Apr 8;42(1):51-62
15066264
J Biol Chem. 2009 Feb 13;284(7):4451-63
19029295
Cell Rep. 2014 Aug 21;8(4):1146-59
25127134
Nature. 2003 Jun 26;423(6943):990-5
12827203
Nature. 1997 Jul 17;388(6639):275-9
9230436
Biochim Biophys Acta. 2005 Dec 30;1746(3):322-33
16019085
Nat Neurosci. 2007 Mar;10 (3):340-7
17259982
Behav Brain Res. 2006 Sep 15;172(1):24-32
16750274
J Biol Chem. 2008 Oct 24;283(43):29385-95
18728013
PLoS One. 2014 Jan 21;9(1):e85217
24465508
J Biol Chem. 2001 Mar 2;276(9):6689-94
11053419
FEBS Lett. 1997 May 5;407(3):313-9
9175875
PLoS One. 2014 Apr 21;9(4):e95835
24752595
Science. 2010 Jan 29;327(5965):547-52
20110498
Genes Dev. 1999 Dec 1;13(23):3125-35
10601038
J Cell Sci. 2010 Jan 1;123(Pt 1):95-106
20016070
Front Cell Neurosci. 2013 Nov 18;7:211
24302895
Science. 1998 Sep 4;281(5382):1515-8
9727979
J Neurosci. 2003 Mar 15;23(6):2228-38
12657682
Nat Neurosci. 2006 Oct;9(10):1257-64
16964251
J Neurochem. 2006 Jul;98(2):330-5
16805828
Science. 2010 Jan 1;327(5961):46-50
20044567
J Cell Biol. 2010 Nov 15;191(4):771-81
21059848
J Biol Chem. 1996 Aug 30;271(35):21604-13
8702948
Biochim Biophys Acta. 2014 Dec;1842(12 Pt B):2561-8
25064589
J Neurosci. 2012 May 30;32(22):7734-44
22649251
Mol Biosyst. 2011 Jan;7(1):52-8
20838685
Glycobiology. 2006 Sep;16(9):19G-22G
16964630
Sci Rep. 2016 Jan 22;5:19679
26795422
Eur J Neurosci. 2006 Dec;24(12):3401-14
17229090
Am J Physiol Cell Physiol. 2009 Mar;296(3):C607-19
19158400
Science. 1996 Mar 29;271(5257):1864-7
8596955