Dlg1-PTEN Interaction Regulates Myelin Thickness to Prevent Damaging Peripheral Nerve Overmyelination

被引：141

作者：

Cotter, Laurent ^{[1
]}

Ozcelik, Murat ^{[1
]}

Jacob, Claire ^{[1
]}

Pereira, Jorge A. ^{[1
]}

Locher, Veronica ^{[1
]}

Baumann, Reto ^{[1
]}

Relvas, Joao B. ^{[1
,2
]}

Suter, Ueli ^{[1
]}

Tricaud, Nicolas ^{[1
]}

机构：

[1] ETH, Inst Cell Biol, Dept Biol, CH-8093 Zurich, Switzerland

[2] Univ Porto, IBMC, P-4150180 Oporto, Portugal

来源：

SCIENCE | 2010年 / 328卷 / 5984期

基金：

瑞士国家科学基金会;

关键词：

NEUREGULIN-1; POLARITY; PHOSPHORYLATION; BINDING; SHEATH; PTEN;

D O I：

10.1126/science.1187735

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The thickness of the myelin sheath that insulates axons is fitted for optimal nerve conduction velocity. Here, we show that, in Schwann cells, mammalian disks large homolog 1 (Dlg1) interacts with PTEN (phosphatase and tensin homolog deleted on chromosome 10) to inhibit axonal stimulation of myelination. This mechanism limits myelin sheath thickness and prevents overmyelination in mouse sciatic nerves. Removing this brake results also in myelin outfoldings and demyelination, characteristics of some peripheral neuropathies. Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance.

引用

页码：1415 / 1418

页数：4

共 24 条

[1] Adey NB, 2000, CANCER RES, V60, P35
[2] Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-tooth type 4B1 neuropathy with myelin outfoldings
Bolis, A
Coviello, S
Bussini, S
Dina, G
Pardini, C
Previtali, SC
Malaguti, M
Morana, P
Del Carro, U
Feltri, ML
Quattrini, A
Wrabetz, L
Bolino, A
[J]. JOURNAL OF NEUROSCIENCE, 2005, 25 (37) : 8567 - 8577
[3] Dlg1, Sec8, and Mtmr2 Regulate Membrane Homeostasis in Schwann Cell Myelination
Bolis, Annalisa
Coviello, Silvia
Visigalli, Ilaria
Taveggia, Carla
Bachi, Angela
Chishti, Athar H.
Hanada, Toshihiko
Quattrini, Angelo
Previtali, Stefano Carlo
Biffi, Alessandra
Bolino, Alessandra
[J]. JOURNAL OF NEUROSCIENCE, 2009, 29 (27) : 8858 - 8870
[4] An animal model for Charcot-Marie-Tooth disease type 4B1
Bonneick, S
Boentert, M
Berger, P
Atanasoski, S
Mantei, N
Wessig, C
Toyka, KV
Young, P
Suter, U
[J]. HUMAN MOLECULAR GENETICS, 2005, 14 (23) : 3685 - 3695
[5] The polarity protein Par-3 directly interacts with p75NTR to regulate myelination
Chan, Jonah R.
Jolicoeur, Christine
Yamauchi, Junji
Elliott, Jimmy
Fawcett, James P.
Ng, Benjamin K.
Cayouette, Michel
[J]. SCIENCE, 2006, 314 (5800) : 832 - 836
[6] Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function
Chen, S
Velardez, MO
Warot, X
Yu, ZX
Miller, SJ
Cros, D
Corfas, G
[J]. JOURNAL OF NEUROSCIENCE, 2006, 26 (12) : 3079 - 3086
[7] E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway
Contreras-Paredes, Adriana
De la Cruz-Hernandez, Erick
Martinez-Ramirez, Imelda
Duenas-Gonzalez, Alfonso
Lizano, Marcela
[J]. VIROLOGY, 2009, 383 (01) : 78 - 85
[8] Constitutively active Akt induces enhanced myelination in the CNS
Flores, Ana I.
Narayanan, S. Priyadarshini
Morse, Emily N.
Shick, H. Elizabeth
Yin, Xinghua
Kidd, Grahame
Avila, Robin L.
Kirschner, Daniel A.
Macklin, Wendy B.
[J]. JOURNAL OF NEUROSCIENCE, 2008, 28 (28) : 7174 - 7183
[9] A dual role of erbB2 in myelination and in expansion of the Schwann cell precursor pool
Garratt, AN
Voiculescu, O
Topilko, P
Charnay, P
Birchmeier, C
[J]. JOURNAL OF CELL BIOLOGY, 2000, 148 (05) : 1035 - 1046
[10] Structure, regulation and function of PKB/AKT - a major therapeutic target
Hanada, M
Feng, JH
Hemmings, BA
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2004, 1697 (1-2): : 3 - 16

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