The node of Ranvier in the peripheral nerve:formation and molecular organization

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

Developmental organization of the nodes of Ranvier in the PNS

Devaux, 2014

Gliomedin interacts with Nfasc186 and induces Nav clustering

Eshed et al, 2005

+ Gldn-FcDRG axons

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

Feinberg et al, 2010

Nfasc186/Gldn complex is crucial for initial Nav clustering

Feinberg et al, 2010

Nfasc186/Gldn complex is crucial for initial Nav clustering

Feinberg et al, 2010

Nfasc186/Gldn complex is crucial for initial Nav clustering

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

3 – Role of nodal cytoskeleton

IV spectrin

Ank-B

Ank-GII/II spectrin

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

I-spectrin compensates for the lack of IV-spectrin at nodes

Ho et al, 2014

4 - Role of paranodal cytoskeleton

IV spectrin

Ank-B

Ank-GII/II 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: