scholarly journals Non-redundant function of dystroglycan and  1 integrins in radial sorting of axons

Development ◽  
2011 ◽  
Vol 138 (18) ◽  
pp. 4025-4037 ◽  
Author(s):  
C. Berti ◽  
L. Bartesaghi ◽  
M. Ghidinelli ◽  
D. Zambroni ◽  
G. Figlia ◽  
...  
Keyword(s):  
Radial Sorting

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 Myelination: all about Rac ‘n’ roll

2007 ◽  
Vol 177 (6) ◽  
pp. 953-955 ◽  
Author(s):  
Jonah R. Chan
Keyword(s):  
Nervous System ◽  
Schwann Cells ◽  
Molecular Mechanisms ◽  
Nerve Bundle ◽  
Effector Molecule ◽  
Downstream Effector ◽  
Rho Family ◽  
Radial Sorting ◽  
Shed Light ◽  
Lamellipodia Formation

During the development of the peripheral nervous system, Schwann cells select individual axons from a nerve bundle and establish a one-to-one relationship through a process termed “radial sorting”. Recent findings identify the Rho family GTPase Rac1 as the downstream effector molecule responsible for process extension and lamellipodia formation in Schwann cells, allowing for proper radial sorting and myelination. These findings begin to shed light on our understanding of the distinct and yet essential molecular mechanisms involved in developmental processes preceding myelination.

scholarly journals The Polarity Protein Pals1 Regulates Radial Sorting of Axons

2015 ◽  
Vol 35 (29) ◽  
pp. 10474-10484 ◽  
Author(s):  
D. R. Zollinger ◽  
K.-J. Chang ◽  
K. Baalman ◽  
S. Kim ◽  
M. N. Rasband
Keyword(s):  
Radial Sorting

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 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.

scholarly journals Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system

2009 ◽  
Vol 185 (1) ◽  
pp. 147-161 ◽  
Author(s):  
Jorge A. Pereira ◽  
Yves Benninger ◽  
Reto Baumann ◽  
Ana Filipa Gonçalves ◽  
Murat Özçelik ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Morphological Changes ◽  
Rho Kinase ◽  
Specific Gene ◽  
Gene Ablation ◽  
Integrin Linked Kinase ◽  
Radial Sorting

During development, Schwann cells (SCs) interpret different extracellular cues to regulate their migration, proliferation, and the remarkable morphological changes associated with the sorting, ensheathment, and myelination of axons. Although interactions between extracellular matrix proteins and integrins are critical to some of these processes, the downstream signaling pathways they control are still poorly understood. Integrin-linked kinase (ILK) is a focal adhesion protein that associates with multiple binding partners to link integrins to the actin cytoskeleton and is thought to participate in integrin and growth factor–mediated signaling. Using SC-specific gene ablation, we report essential functions for ILK in radial sorting of axon bundles and in remyelination in the peripheral nervous system. Our in vivo and in vitro experiments show that ILK negatively regulates Rho/Rho kinase signaling to promote SC process extension and to initiate radial sorting. ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B.

scholarly journals Conditional disruption of β1 integrin in Schwann cells impedes interactions with axons

2002 ◽  
Vol 156 (1) ◽  
pp. 199-210 ◽  
Author(s):  
M. Laura Feltri ◽  
Diana Graus Porta ◽  
Stefano C. Previtali ◽  
Alessandro Nodari ◽  
Barbara Migliavacca ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Muscular Dystrophy ◽  
Schwann Cells ◽  
Congenital Muscular Dystrophy ◽  
Laminin Receptor ◽  
Β1 Integrin ◽  
Laminin Receptors ◽  
Α6β4 Integrin ◽  
Radial Sorting ◽  
Dystrophic Mice

In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell–specific disruption of β1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. β1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and α6β4 integrin. These data suggest that β1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.

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