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Nav/Nfasc186
Kv7.2/7.3
NrCAM Gldn
Ank-G
IV-spectrin
Schwann cell microvilli
axon
PNS node
Ranvier, 1878
PNS Paranode
Nfasc155Contactin-1
axon
Caspr-1
II-spectrin/II-spectrin
4.1B
Ank-Bglia
1 - Cell adhesion molecules at the nodes of Ranvier
Alteration of axoglial contact in demyelinating neuropathy
Lonigro and Devaux, 2009
Caspr-1/NavControl 9 dpi 13 dpi
Control 9 dpi 13 dpi
CNTN1/Gldn
Hirano,1969
2 - Implication of cell adhesion molecules at paranodes
PNS Paranode
Nfasc155Contactin-1
axon
Caspr-1
II-spectrin/II-spectrin
4.1B
Ank-Bglia
Caspr-1/CNTN1/Nfasc155 complex is essential for the formation of septate-like junctions
Bhat et al, 2001
Cas
pr1
-/-W
T
Bhat et al, 2001
Nfasc155/CNTN1/Caspr-1 complex is not essential for node formation
CN
TN1/
Cas
pr-1
NF/
Cas
pr-1
Caspr-/-WT
Sherman et al, 2005
Nodal and paranodal axo-glial contacts are essential for Nav channel clustering
Nfasc +/+ Nfasc -/-
CNTN1/Caspr1/DP116
Nfasc/Caspr1/DP116
Nav/MBP
NrCAM/MBP
Nfasc -/-
Nfasc186 -/-
WT
Role of Ankyrin-G in Nav channel clustering
Ank-R
Ank-G
WT
Ank-G -/-
Ho et al, 2014
Ank3fl/fl
Avil-Cre; Ank3fl/fl
Ankyrin-G/R deletion induces the loss of Nav channel clustering
WT
Ank-G -/- ; Ank-R-/-
Ho et al, 2014
Avil-Cre; Ank3fl/fl
Avil-Cre; Ank3fl/fl; Ank1pale/pale
Devaux, 2010
IV-spectrin regulates ion channel clustering at nodes
Devaux, 2010
WT
qv3J
Kv7.2/CNTN1
Kv7.2/CNTN1
WT
qv3J
Kv7.2
Ank-RI-spectrin
Devaux, 2010
Ank-B and II-spectrin are not essential for node or paranode formation
Zhang et al, 2013
Devaux, 2010Amor et al, 2016
Nfasc186 +/+ (Nfascfl/fl)
II/II spectrin
WT
Nfasc186 -/-
?
Nfasc186 -/- (Avil-Cre/Nfascfl/fl)
II/II spectrin
Caspr PanNF
Is paranodal cytoskelon important for Nav clustering ?
Devaux, 2010
II-spectrin mediates the paranodal fence
Amor et al, 2016
Nfascfl/fl
Spnb2fl/fl
Avil-CreNfascfl/fl
Spnb2fl/fl
WT
Nfasc186 -/- ; Spnb2 -/-
Nfascfl/fl
Spnb2fl/fl
Avil-CreNfascfl/fl
Spnb2fl/fl
Nav/Caspr/
Ank-G/PanNF/
Concluding remarks:
PNS node formation :
Axo-glial contact
Cytoskelon
What mechanisms are responsible for paranode and node specialization?
Development
CHRU de Montpellier, FRANCEGuillaume Taieb, Pierre Labauge, Pauline Malissart
SPAINIsabel Illa and Luis Querol
UK ISRAELPeter Brophy Elior Peles
ITALYAndrea Cortese, Angela Berardinelli, and Diego Franciotta
USAAlex Gow
JAPANYumako Miura, Kenji Sekiguchi, Norito Kokubun, and Nobuhiro Yuki
CRN2M, Marseille, FRANCEConstance MansoMaya BelghaziMourad MekaoucheMaryline LabasqueCatherine Faivre-SarrailhAurélie Lonigro
Institut du fer à Moulin, Paris, FRANCELaurence Goutebroze
CHU Limoges, FRANCEJean-Michel Vallat
CHU Timone, Marseille, FRANCEShahram Attarian, Emilien Delmont
Hôpital Salpêtrière, Paris, FRANCEKarine Viala, Thierry Maisonobe
Acknowledgements: