TY - JOUR
T1 - Precise Spatiotemporal Control of Nodal Na+ Channel Clustering by Bone Morphogenetic Protein-1/Tolloid-like Proteinases
AU - Eshed-Eisenbach, Yael
AU - Devaux, Jerome
AU - Vainshtein, Anna
AU - Golani, Ofra
AU - Lee, Se-Jin
AU - Feinberg, Konstantin
AU - Sukhanov, Natasha
AU - Greenspan, Daniel S.
AU - Susuki, Keiichiro
AU - Rasband, Matthew N.
AU - Peles, Elior
N1 - We would like to thank Michael Tsoory for his expert advice and support. This work was supported by research grants from the Israel Science Foundation, the Binational Science Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the National American Brain Foundation, the Lilly Fulop Fund for Multiple Sclerosis Research, the Estate of David Georges Eskinazi, Dahlia and Philip Lawee, Gary Clayman, Ellie Adiel, Agence Nationale de la Recherche (ACAMIN; E.P. and J.D.) under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, and from Association Française contre les Myopathies (grant 21532 to J.D.). E.P. is the incumbent of the Hanna Hertz Professorial Chair for Multiple Sclerosis and Neuroscience. Author contributions - Conceptualization and Writing, Y.E.-E. and E.P.; Methodology, Investigation, and Analysis, Y.E.-E., K.F., A.V., N.S., K.S., and J.D.; Resources, O.G., S.J.-L., M.N.R., and D.S.G.; Supervision, E.P.
PY - 2020/6/3
Y1 - 2020/6/3
N2 - During development of the peripheral nervous system (PNS), Schwann-cell-secreted gliomedin induces the clustering of Na+ channels at the edges of each myelin segment to form nodes of Ranvier. Here we show that bone morphogenetic protein-1 (BMP1)/Tolloid (TLD)-like proteinases confine Na+ channel clustering to these sites by negatively regulating the activity of gliomedin. Eliminating the Bmp1/TLD cleavage site in gliomedin or treating myelinating cultures with a Bmp1/TLD inhibitor results in the formation of numerous ectopic Na+ channel clusters along axons that are devoid of myelin segments. Furthermore, genetic deletion of Bmp1 and Tll1 genes in mice using a Schwann-cell-specific Cre causes ectopic clustering of nodal proteins, premature formation of heminodes around early ensheathing Schwann cells, and altered nerve conduction during development. Our results demonstrate that by inactivating gliomedin, Bmp1/TLD functions as an additional regulatory mechanism to ensure the correct spatial and temporal assembly of PNS nodes of Ranvier.
AB - During development of the peripheral nervous system (PNS), Schwann-cell-secreted gliomedin induces the clustering of Na+ channels at the edges of each myelin segment to form nodes of Ranvier. Here we show that bone morphogenetic protein-1 (BMP1)/Tolloid (TLD)-like proteinases confine Na+ channel clustering to these sites by negatively regulating the activity of gliomedin. Eliminating the Bmp1/TLD cleavage site in gliomedin or treating myelinating cultures with a Bmp1/TLD inhibitor results in the formation of numerous ectopic Na+ channel clusters along axons that are devoid of myelin segments. Furthermore, genetic deletion of Bmp1 and Tll1 genes in mice using a Schwann-cell-specific Cre causes ectopic clustering of nodal proteins, premature formation of heminodes around early ensheathing Schwann cells, and altered nerve conduction during development. Our results demonstrate that by inactivating gliomedin, Bmp1/TLD functions as an additional regulatory mechanism to ensure the correct spatial and temporal assembly of PNS nodes of Ranvier.
UR - http://www.scopus.com/inward/record.url?scp=85083019761&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2020.03.001
DO - 10.1016/j.neuron.2020.03.001
M3 - مقالة
SN - 0896-6273
VL - 106
SP - 806
EP - 815
JO - Neuron
JF - Neuron
IS - 5
ER -