ArticlePLoS biology2017
Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Molecular Mediators Associated With Myelination, Demyelination, and Remyelination in the Peripheral Nervous System.Journal of the peripheral nervous system : JPNS · 2026Review
- Expanding the phenotypic spectrum of LAMA2-related disorders: Axonal neuropathy in the absence of muscular dystrophy.Journal of human genetics · 2026Article
- Roles and therapeutic prospects of the laminin family in disorders of the nervous system.Journal of translational medicine · 2026Review
- Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination.Cells · 2025Article
- The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.Cell reports · 2025Article
- Schwann Cell Development and Myelination.Cold Spring Harbor perspectives in biology · 2024Review
- Structure, ligands, and roles of GPR126/ADGRG6 in the development and diseases.Genes & diseases · 2024Review
- A Novel Form of Neuregulin 1 Type III Caused by N-Terminal Processing.Biomolecules · 2023Article
- Review
- Models and methods to study Schwann cells.Journal of anatomy · 2022Review
- Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes.European archives of psychiatry and clinical neuroscience · 2022Article
- Amelioration of muscle and nerve pathology of Lama2-related dystrophy by AAV9-laminin-αLN linker protein.JCI insight · 2022Article
- Beyond Wrapping: Canonical and Noncanonical Functions of Schwann Cells.Annual review of neuroscience · 2022Review
- ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve.iScience · 2022Article
- Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Review: Myelin clearance is critical for regeneration after peripheral nerve injury.Frontiers in neurology · 2022Review
- A physical perspective to understand myelin II: The physical origin of myelin development.Frontiers in neuroscience · 2022Article
- Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression.Frontiers in behavioral neuroscience · 2022Review
- Wrestling and Wrapping: A Perspective on SUMO Proteins in Schwann Cells.Biomolecules · 2021Review
- Schwann cell interactions during the development of the peripheral nervous system.Developmental neurobiology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination. Lm211 can inhibit Nrg1III by limiting protein kinase A (PKA) activation, which is required to initiate myelination. We provide evidence that excessive PKA activation amplifies promyelinating signals downstream of neuregulin, including direct activation of the neuregulin receptor ErbB2 and its effector Grb2-Associated Binder-1 (Gab1), thereby elevating the expression of the key transcription factors Oct6 and early growth response protein 2 (Egr2). The inhibitory effect of Lm211 is seen only in fibers of small caliber. These data may explain why hereditary neuropathies associated with decreased laminin function are characterized by focally thick and redundant myelin.
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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.