ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
The actin-severing protein cofilin is downstream of neuregulin signaling and is essential for Schwann cell myelination.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Label-free proteomic profiling identifies ECM-related alterations across regeneration states in human peripheral axonal neuropathies.Journal of physiology and biochemistry · 2026Article
- Schwann Cell Development and Myelination.Cold Spring Harbor perspectives in biology · 2024Review
- Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells.Molecular cancer therapeutics · 2023Article
- Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum-Does the Common Pathophysiological Pathway Exist?Cancers · 2023Review
- Imbalance of NRG1-ERBB2/3 signalling underlies altered myelination in Charcot-Marie-Tooth disease 4H.Brain : a journal of neurology · 2023Article
- Review
- ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve.iScience · 2022Article
- Asparaginyl endopeptidase protects against podocyte injury in diabetic nephropathy through cleaving cofilin-1.Cell death & disease · 2022Article
- Fibulin 5, a human Wharton's jelly-derived mesenchymal stem cells-secreted paracrine factor, attenuates peripheral nervous system myelination defects through the Integrin-RAC1 signaling axis.Stem cells (Dayton, Ohio) · 2020Article
- Article
- The Actin Cytoskeleton in Myelinating Cells.Neurochemical research · 2020Review
- Review
- Article
- Role of Cofilin in Alzheimer's Disease.Frontiers in cell and developmental biology · 2020Review
- Article
- Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation.The Journal of biological chemistry · 2018Article
- Phenotypic and Functional Characteristics of Human Schwann Cells as Revealed by Cell-Based Assays and RNA-SEQ.Molecular neurobiology · 2018Article
- Hyperactivity of Rac1-GTPase pathway impairs neuritogenesis of cortical neurons by altering actin dynamics.Scientific reports · 2018Article
- Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin.Frontiers in physiology · 2018Article
- Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells.International journal of molecular sciences · 2016Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Myelination is a complex process requiring coordination of directional motility and an increase in glial cell size to generate a multilamellar myelin sheath. Regulation of actin dynamics during myelination is poorly understood. However, it is known that myelin thickness is related to the abundance of neuregulin-1 (NRG1) expressed on the axon surface. Here we identify cofilin1, an actin depolymerizing and severing protein, as a downstream target of NRG1 signaling in rat Schwann cells (SCs). In isolated SCs, NRG1 promotes dephosphorylation of cofilin1 and its upstream regulators, LIM kinase (LIMK) and Slingshot-1 phosphatase (SSH1), leading to cofilin1 activation and recruitment to the leading edge of the plasma membrane. These changes are associated with rapid membrane expansion yielding a 35-50% increase in SC size within 30 min. Cofilin1-deficient SCs increase phosphorylation of ErbB2, ERK, focal adhesion kinase, and paxillin in response to NRG1, but fail to increase in size possibly due to stabilization of unusually long focal adhesions. Cofilin1-deficient SCs cocultured with sensory neurons do not myelinate. Ultrastructural analysis reveals that they unsuccessfully segregate or engage axons and form only patchy basal lamina. After 48 h of coculturing with neurons, cofilin1-deficient SCs do not align or elongate on axons and often form adhesions with the underlying substrate. This study identifies cofilin1 and its upstream regulators, LIMK and SSH1, as end targets of a NRG1 signaling pathway and demonstrates that cofilin1 is necessary for dynamic changes in the cytoskeleton needed for axon engagement and myelination by SCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.