scholarly journals ErbB signaling has a role in radial sorting independent of Schwann cell number

Glia ◽  
2011 ◽  
Vol 59 (7) ◽  
pp. 1047-1055 ◽  
Author(s):  
Alya R. Raphael ◽  
David A. Lyons ◽  
William S. Talbot
Keyword(s):  
Schwann Cell ◽  
Cell Number ◽  
Erbb Signaling ◽  
Radial Sorting

scholarly journals Neuregulin 1 Type III/ErbB Signaling Is Crucial for Schwann Cell Colonization of Sympathetic Axons

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28692 ◽  
Author(s):  
Stephan Heermann ◽  
Julia Schmücker ◽  
Ursula Hinz ◽  
Michael Rickmann ◽  
Tilmann Unterbarnscheidt ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Neuregulin 1 ◽  
Type Iii ◽  
Erbb Signaling ◽  
Cell Colonization

scholarly journals The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development

2009 ◽  
Vol 106 (39) ◽  
pp. 16704-16709 ◽  
Author(s):  
K. S. Grossmann ◽  
H. Wende ◽  
F. E. Paul ◽  
C. Cheret ◽  
A. N. Garratt ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Tyrosine Phosphatase ◽  
Cell Development ◽  
Neuregulin 1 ◽  
Erbb Signaling ◽  
Schwann Cell Development

scholarly journals Jab1 regulates Schwann cell proliferation and axonal sorting through p27

2013 ◽  
Vol 211 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Emanuela Porrello ◽  
Cristina Rivellini ◽  
Giorgia Dina ◽  
Daniela Triolo ◽  
Ubaldo Del Carro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cycle Progression ◽  
Cell Number ◽  
Cycle Progression ◽  
Neuregulin 1 ◽  
Regulatory Molecule ◽  
Axonal Sorting

Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin211– and, possibly, neuregulin 1 (Nrg1)–derived signals. However, how these signals are integrated in Schwann cells is largely unknown. We now report that the nuclear Jun activation domain–binding protein 1 (Jab1) may transduce laminin211 signals to regulate Schwann cell number and differentiation during axonal sorting. Mice with inactivation of Jab1 in Schwann cells develop a dysmyelinating neuropathy with axonal sorting defects. Loss of Jab1 increases p27 levels in Schwann cells, which causes defective cell cycle progression and aberrant differentiation. Genetic down-regulation of p27 levels in Jab1-null mice restores Schwann cell number, differentiation, and axonal sorting and rescues the dysmyelinating neuropathy. Thus, Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation. Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies.

scholarly journals Schwann cell-specific deletion of the endosomal PI 3-kinase Vps34 leads to delayed radial sorting of axons, arrested myelination, and abnormal ErbB2-ErbB3 tyrosine kinase signaling

Glia ◽  
2017 ◽  
Vol 65 (9) ◽  
pp. 1452-1470 ◽  
Author(s):  
Anne M. Logan ◽  
Anna E. Mammel ◽  
Danielle C. Robinson ◽  
Andrea L. Chin ◽  
Alec F. Condon ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Tyrosine Kinase ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling ◽  
Radial Sorting ◽  
Specific Deletion

scholarly journals CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria A. Eichel ◽  
Vasiliki-Ilya Gargareta ◽  
Elisa D’Este ◽  
Robert Fledrich ◽  
Theresa Kungl ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Nerve Conduction ◽  
Radial Growth ◽  
Transmembrane Domain ◽  
Sensory Nerve ◽  
Label Free ◽  
Sensory Responses ◽  
Radial Sorting ◽  
Dependent Mechanism

Abstract The velocity of nerve conduction is moderately enhanced by larger axonal diameters and potently sped up by myelination of axons. Myelination thus allows rapid impulse propagation with reduced axonal diameters; however, no myelin-dependent mechanism has been reported that restricts radial growth of axons. By label-free proteomics, STED-microscopy and cryo-immuno electron-microscopy we here identify CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) as a myelin protein specifically localized to the Schwann cell membrane exposed to the axon. We find that disruption of Cmtm6-expression in Schwann cells causes a substantial increase of axonal diameters but does not impair myelin biogenesis, radial sorting or integrity of axons. Increased axonal diameters correlate with accelerated sensory nerve conduction and sensory responses and perturbed motor performance. These data show that Schwann cells utilize CMTM6 to restrict the radial growth of axons, which optimizes nerve function.

scholarly journals FAK is required for axonal sorting by Schwann cells

2007 ◽  
Vol 176 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Matthew Grove ◽  
Noboru H. Komiyama ◽  
Klaus-Armin Nave ◽  
Seth G. Grant ◽  
Diane L. Sherman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Number ◽  
Erbb Receptor ◽  
Erbb2 Receptor ◽  
Transduction Mechanisms ◽  
Axonal Sorting ◽  
Developing Nervous System ◽  
Stimulate Cell Proliferation

Signaling by laminins and axonal neuregulin has been implicated in regulating axon sorting by myelin-forming Schwann cells. However, the signal transduction mechanisms are unknown. Focal adhesion kinase (FAK) has been linked to α6β1 integrin and ErbB receptor signaling, and we show that myelination by Schwann cells lacking FAK is severely impaired. Mutant Schwann cells could interdigitate between axon bundles, indicating that FAK signaling was not required for process extension. However, Schwann cell FAK was required to stimulate cell proliferation, suggesting that amyelination was caused by insufficient Schwann cells. ErbB2 receptor and AKT were robustly phosphorylated in mutant Schwann cells, indicating that neuregulin signaling from axons was unimpaired. These findings demonstrate the vital relationship between axon defasciculation and Schwann cell number and show the importance of FAK in regulating cell proliferation in the developing nervous system.

scholarly journals Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

2007 ◽  
Vol 177 (6) ◽  
pp. 1051-1061 ◽  
Author(s):  
Yves Benninger ◽  
Tina Thurnherr ◽  
Jorge A. Pereira ◽  
Sven Krause ◽  
Xunwei Wu ◽  
...  
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Rho Gtpases ◽  
Cell Biology ◽  
System Development ◽  
Nervous System Development ◽  
Conditional Gene Targeting ◽  
Radial Sorting

During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles.

scholarly journals Distinct roles for the Charcot-Marie-Tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination

2019 ◽  
Author(s):  
Anna E. Mammel ◽  
Katherine C. Delgado ◽  
Andrea L. Chin ◽  
Alec F. Condon ◽  
Jo Q. Hill ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Protein Complexes ◽  
Endosomal Trafficking ◽  
Rab Gtpases ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Type ◽  
Perinatal Lethality ◽  
Radial Sorting ◽  
Redundant Functions

ABSTRACTThe form of Charcot-Marie-Tooth type 4B (CMT4B) disease caused by mutations in myotubularin-related 5 (MTMR5; also called SET Binding Factor 1; SBF1) shows a spectrum of axonal and demyelinating nerve phenotypes. This contrasts with the CMT4B subtypes caused by MTMR2 or MTMR13 (SBF2) mutations, which are characterized by myelin outfoldings and classic demyelination. Thus, it is unclear whether MTMR5 plays an analogous or distinct role from that of its homolog, MTMR13, in the peripheral nervous system (PNS). MTMR5 and MTMR13 are pseudophosphatases predicted to regulate endosomal trafficking by activating Rab GTPases and binding to the phosphoinositide 3-phosphatase MTMR2. In the mouse PNS, Mtmr2 was required to maintain wild type levels of Mtmr5 and Mtmr13, suggesting that these factors function in discrete protein complexes. Genetic elimination of both Mtmr5 and Mtmr13 in mice led to perinatal lethality, indicating that the two proteins have partially redundant functions during embryogenesis. Loss of Mtmr5 in mice did not cause CMT4B-like myelin outfoldings. However, adult Mtmr5-/- mouse nerves contained fewer myelinated axons than control nerves, likely as a result of axon radial sorting defects. Mtmr5 levels were highest during axon radial sorting, whereas Mtmr13 levels rose as myelin formed, and remained high through adulthood. Our findings suggest that Mtmr5 and Mtmr13 ensure proper axon radial sorting and Schwann cell myelination, respectively, perhaps through their direct interactions with Mtmr2. This study enhances our understanding of the non-redundant roles of the endosomal regulators MTMR5 and MTMR13 during normal peripheral nerve development and disease.

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