Electron tomography of paranodal septate-like junctions and the associated axonal and glial cytoskeletons in the central nervous system.
The polarized domains of myelinated axons are specifically organized to maximize the efficiency of saltatory conduction. The paranodal region is directly adjacent to the node of Ranvier and contains specialized septate-like junctions that provide adhesion between axons and glial cells and that constitute a lateral diffusion barrier for nodal components. To complement and extend earlier studies on the peripheral nervous system, electron tomography was used to image paranodal regions from the central nervous system (CNS). Our three-dimensional reconstructions revealed short filamentous linkers running directly from the septate-like junctions to neurofilaments, microfilaments, and organelles within the axon. The intercellular spacing between axons and glia was measured to be 7.4 ± 0.6 nm, over twice the value previously reported in the literature (2.5-3.0 nm). Averaging of individual junctions revealed a bifurcated structure in the intercellular space that is consistent with a dimeric complex of cell adhesion molecules composing the septate-like junction. Taken together, these findings provide new insight into the structural organization of CNS paranodes and suggest that, in addition to providing axo-glial adhesion, cytoskeletal linkage to the septate-like junctions may be required to maintain axonal domains and to regulate organelle transport in myelinated axons.
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Andrea
A
Nans
Steven
S
Einheber
James L
JL
Salzer
David L
DL
Stokes
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D002490:Central Nervous System / Q000166:cytology*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D055032:Electron Microscope Tomography / Q000379:methods*; D007365:Intercellular Junctions / Q000648:ultrastructure*; D051379:Mice; D016900:Neurofilament Proteins / Q000378:metabolism / Q000648:ultrastructure; D009457:Neuroglia / Q000166:cytology* / Q000648:ultrastructure
D016900:Neurofilament Proteins
J Cell Biol. 1997 Dec 15;139(6):1495-506
9396755
J Neurosci. 2004 Aug 18;24(33):7230-40
15317849
Neuron. 2003 Oct 9;40(2):297-318
14556710
J Neurocytol. 1976 Dec;5(6):731-45
1087339
Neuroscience. 1976 Jun;1(3):181-90
11370229
Neuron. 1997 Aug;19(2):319-31
9292722
Nat Rev Mol Cell Biol. 2004 Apr;5(4):271-81
15071552
Science. 2003 Oct 3;302(5642):109-13
14526082
Science. 2006 Aug 18;313(5789):944-8
16917055
Histochem Cell Biol. 2000 Jan;113(1):1-18
10664064
Curr Biol. 2002 Feb 5;12(3):217-20
11839274
J Neurocytol. 1982 Dec;11(6):861-6
6185646
J Biol Chem. 1982 Aug 25;257(16):9781-7
7107591
J Neurosci. 2006 Mar 8;26(10):2599-613
16525039
J Cell Biol. 1980 Feb;84(2):261-80
7380883
J Neurosci. 1986 Oct;6(10):2977-86
3531427
J Comp Neurol. 2000 Nov 20;427(3):340-50
11054697
J Cell Biol. 2007 Jun 4;177(5):857-70
17548513
Nature. 1966 May 14;210(5037):757-8
5961213
Cell Tissue Res. 1974 May 8;148(4):577-86
4836650
J Ultrastruct Res. 1961 Aug;5:374-87
13889815
J Cell Sci. 1982 Aug;56:245-62
7166566
J Neurosci. 2006 May 10;26(19):5230-9
16687515
J Neurosci. 2000 Dec 15;20(24):9135-44
11124991
Annu Rev Genet. 2001;35:747-84
11700298
Curr Opin Neurobiol. 2003 Oct;13(5):552-9
14630217
J Cell Biol. 1981 Sep;90(3):631-42
6169732
Brain. 2006 Dec;129(Pt 12):3173-85
17041241
J Neurosci. 2010 Feb 17;30(7):2480-9
20164332
J Cell Biol. 1967 Aug;34(2):555-67
6035645
Physiol Rev. 2001 Jul;81(3):1353-92
11427698
J Cell Biol. 2007 Feb 12;176(4):509-19
17283186
J Cell Biol. 1966 Aug;30(2):269-97
5968972
J Electron Microsc (Tokyo). 1968;17(2):158-9
4177281
Curr Opin Neurobiol. 2000 Oct;10(5):558-65
11084317
Brain. 2003 Jul;126(Pt 7):1638-49
12805111
Lancet. 2002 Apr 6;359(9313):1221-31
11955556
J Neurocytol. 1991 Aug;20(8):667-81
1719139
Semin Cell Dev Biol. 2009 Oct;20(8):920-30
19664718
J Cell Biol. 2004 Sep 27;166(7):983-90
15381686
J Neurosci Res. 2009 Nov 15;87(15):3250-8
19224642
Biotechniques. 2006 Aug;41(2):137, 139, 141 passim
16925014
Brain Res. 1973 Aug 17;58(1):1-24
4199897
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5137-42
16551741
J Biol Chem. 2007 Mar 2;282(9):6548-55
17197442
Neuron Glia Biol. 2006 Aug;2(3):165-74
17460780
Mol Biol Cell. 2005 Sep;16(9):4243-55
16000374
J Struct Biol. 1996 Jan-Feb;116(1):71-6
8742726
Ultramicroscopy. 2006 Feb;106(3):240-54
16137829
Exp Biol Med (Maywood). 2008 Apr;233(4):394-400
18367627
J Cell Biol. 1984 Jul;99(1 Pt 2):212s-221s
6378920
J Cell Sci. 2005 Dec 1;118(Pt 23):5411-9
16306220
J Struct Biol. 2008 Mar;161(3):469-80
18096402
J Struct Biol. 1997 Dec;120(3):343-52
9441937