 |
 Previous Article | Next Article 
The Journal of Neuroscience, June 15, 2000, 20(12):4635-4645
Axonal Regulation of Schwann Cell Proliferation and Survival and
the Initial Events of Myelination Requires PI 3-Kinase Activity
Patrice
Maurel1 and
James
L.
Salzer1, 2, 3
Departments of 1 Cell Biology, 2 Neurology,
and the 3 Kaplan Cancer Center, New York University Medical
Center, New York, New York 10016
In this report, we have investigated the signaling pathways that
are activated by, and mediate the effects of, the neuregulins and
axonal contact in Schwann cells. Phosphatidylinositol 3-kinase (PI
3-kinase) and mitogen-activated protein kinase kinase (MAPK kinase) are strongly activated in Schwann cells by glial growth factor
(GGF), a soluble neuregulin, and by contact with neurite membranes;
both kinase activities are also detected in Schwann cell-DRG neuron
cocultures. Inhibition of the PI 3-kinase, but not the MAP
kinase, pathway reversibly inhibited Schwann cell proliferation
induced by GGF and neurites. Cultured Schwann cells undergo apoptosis
after serum deprivation and can be rescued by GGF or contact with
neurites; these survival effects were also blocked by inhibition of PI
3-kinase. Finally, we have examined the role of these signaling
pathways in Schwann cell differentiation in cocultures. At early stages
of coculture, inhibition of PI 3-kinase, but not MAPK kinase, blocked
Schwann cell elongation and subsequent myelination but did not affect
laminin deposition. Later, after Schwann cells established a one-to-one
relationship with axons, inhibition of PI 3-kinase did not block myelin
formation, but the myelin sheaths that formed were shorter, and the
rate of myelin protein accumulation was markedly decreased. PI 3-kinase inhibition had no observable effect on the maintenance of myelin sheaths in mature myelinated cocultures. These results indicate that
activation of PI 3-kinase by axonal factors, including the neuregulins,
promotes Schwann cell proliferation and survival and implicate PI
3-kinase in the early events of myelination.
Key words:
Schwann cell; PI 3-kinase; MAP kinase; proliferation; survival; myelination; signaling pathways
Copyright © 2000 Society for Neuroscience 0270-6474/00/20124635-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. A. Pereira, Y. Benninger, R. Baumann, A. F. Goncalves, M. Ozcelik, T. Thurnherr, N. Tricaud, D. Meijer, R. Fassler, U. Suter, et al.
Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system
J. Cell Biol.,
April 6, 2009;
185(1):
147 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Francis, J. Martinez, W. Liu, T. Nguyen, A. Ayer, J. Fine, D. Zochodne, L. R. Hanson, W. H. Frey II, and C. Toth
Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy
Diabetes,
April 1, 2009;
58(4):
934 - 945.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Freidin, S. Asche, T. A. Bargiello, M. V. L. Bennett, and C. K. Abrams
Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1)
PNAS,
March 3, 2009;
106(9):
3567 - 3572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-C. Kao, H. Wu, J. Xie, C.-P. Chang, J. A. Ranish, I. A. Graef, and G. R. Crabtree
Calcineurin/NFAT Signaling Is Required for Neuregulin-Regulated Schwann Cell Differentiation
Science,
January 30, 2009;
323(5914):
651 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wakatsuki, N. Yumoto, K. Komatsu, T. Araki, and A. Sehara-Fujisawa
Roles of Meltrin-{beta}/ADAM19 in Progression of Schwann Cell Differentiation and Myelination during Sciatic Nerve Regeneration
J. Biol. Chem.,
January 30, 2009;
284(5):
2957 - 2966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Flores, S. P. Narayanan, E. N. Morse, H. E. Shick, X. Yin, G. Kidd, R. L. Avila, D. A. Kirschner, and W. B. Macklin
Constitutively Active Akt Induces Enhanced Myelination in the CNS
J. Neurosci.,
July 9, 2008;
28(28):
7174 - 7183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. LeBlanc, S.-W. Jang, R. M. Ward, L. Wrabetz, and J. Svaren
Direct Regulation of Myelin Protein Zero Expression by the Egr2 Transactivator
J. Biol. Chem.,
March 3, 2006;
281(9):
5453 - 5460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Atanasoski, S. S. Scherer, E. Sirkowski, D. Leone, A. N. Garratt, C. Birchmeier, and U. Suter
ErbB2 Signaling in Schwann Cells Is Mostly Dispensable for Maintenance of Myelinated Peripheral Nerves and Proliferation of Adult Schwann Cells after Injury
J. Neurosci.,
February 15, 2006;
26(7):
2124 - 2131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Y. Fu, F. C. F. Ip, W.-Y. Fu, J. Cheung, J. H. Wang, W.-H. Yung, and N. Y. Ip
Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice
PNAS,
October 18, 2005;
102(42):
15224 - 15230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-M. Yu, M. L. Feltri, L. Wrabetz, S. Strickland, and Z.-L. Chen
Schwann Cell-Specific Ablation of Laminin {gamma}1 Causes Apoptosis and Prevents Proliferation
J. Neurosci.,
May 4, 2005;
25(18):
4463 - 4472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Dobrowsky, S. Rouen, and C. Yu
Altered Neurotrophism in Diabetic Neuropathy: Spelunking the Caves of Peripheral Nerve
J. Pharmacol. Exp. Ther.,
May 1, 2005;
313(2):
485 - 491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Hempstead
Coupling neurotrophins to cell migration through selective guanine nucleotide exchange factor activation
PNAS,
April 19, 2005;
102(16):
5645 - 5646.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ogata, S. Iijima, S. Hoshikawa, T. Miura, S.-i. Yamamoto, H. Oda, K. Nakamura, and S. Tanaka
Opposing Extracellular Signal-Regulated Kinase and Akt Pathways Control Schwann Cell Myelination
J. Neurosci.,
July 28, 2004;
24(30):
6724 - 6732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. V. Michailov, M. W. Sereda, B. G. Brinkmann, T. M. Fischer, B. Haug, C. Birchmeier, L. Role, C. Lai, M. H. Schwab, and K.-A. Nave
Axonal Neuregulin-1 Regulates Myelin Sheath Thickness
Science,
April 30, 2004;
304(5671):
700 - 703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. V. Melendez-Vasquez, S. Einheber, and J. L. Salzer
Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains
J. Neurosci.,
April 21, 2004;
24(16):
3953 - 3963.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, M. I. Gonzalez, J. L. Meinkoth, J. Field, M. G. Kazanietz, and G. I. Tennekoon
Lysophosphatidic Acid Promotes Survival and Differentiation of Rat Schwann Cells
J. Biol. Chem.,
March 7, 2003;
278(11):
9585 - 9591.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Akiyama, C. Radtke, and J. D. Kocsis
Remyelination of the Rat Spinal Cord by Transplantation of Identified Bone Marrow Stromal Cells
J. Neurosci.,
August 1, 2002;
22(15):
6623 - 6630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Winseck, J. Caldero, D. Ciutat, D. Prevette, S. A. Scott, G. Wang, J. E. Esquerda, and R. W. Oppenheim
In Vivo Analysis of Schwann Cell Programmed Cell Death in the Embryonic Chick: Regulation by Axons and Glial Growth Factor
J. Neurosci.,
June 1, 2002;
22(11):
4509 - 4521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Chuenkova, F. B. Furnari, W. K. Cavenee, and M. A. Pereira
Trypanosoma cruzi trans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling
PNAS,
July 24, 2001;
(2001)
161298398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. O'Shea, K. Johnson, R. Clark, M. X. Sliwkowski, and S. L. Erickson
Effects of in Vivo Heregulin {beta}1 Treatment in Wild-Type and ErbB Gene-Targeted Mice Depend on Receptor Levels and Pregnancy
Am. J. Pathol.,
May 1, 2001;
158(5):
1871 - 1880.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. HALL
Nerve Repair: A Neurobiologist's View
J Hand Surg Eur Vol.,
April 1, 2001;
26(2):
129 - 136.
[PDF]
|
|
|
|
|
|
|
G. Zanazzi, S. Einheber, R. Westreich, M.-J. Hannocks, D. Bedell-Hogan, M. A. Marchionni, and J. L. Salzer
Glial Growth Factor/Neuregulin Inhibits Schwann Cell Myelination and Induces Demyelination
J. Cell Biol.,
March 19, 2001;
152(6):
1289 - 1300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Y. Wang, S. J. Miller, and D. L. Falls
The N-terminal Region of Neuregulin Isoforms Determines the Accumulation of Cell Surface and Released Neuregulin Ectodomain
J. Biol. Chem.,
January 19, 2001;
276(4):
2841 - 2851.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Chuenkova, F. B. Furnari, W. K. Cavenee, and M. A. Pereira
Trypanosoma cruzi trans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling
PNAS,
August 14, 2001;
98(17):
9936 - 9941.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
