دورية أكاديمية
أعرض في EDS

Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration.

التفاصيل البيبلوغرافية
العنوان: Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration.
المؤلفون: Pinto-Costa R; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and.; Graduate Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal., Sousa SC; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and.; Graduate Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal., Leite SC; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and., Nogueira-Rodrigues J; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and.; Graduate Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal., Ferreira da Silva T; NeuroLipid Biology Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Porto, Portugal., Machado D; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and., Marques J; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and., Costa AC; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and., Liz MA; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and., Bartolini F; Department of Pathology and Cell Biology, Columbia University, New York, New York, USA., Brites P; NeuroLipid Biology Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Porto, Portugal., Costell M; Department of Biochemistry and Molecular Biology and Estructura de Reserca Interdisciplinar en Biotecnologia i Biomedicina, Universitat de València, Valencia, Spain., Fässler R; Department of Molecular Medicine, Max Plank Institute of Biochemistry, Martinsried, Germany., Sousa MM; Nerve Regeneration Group, Program in Neurobiology and Neurologic Disorders, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Inovação e Investigação em Saúde, and.
المصدر: The Journal of clinical investigation [J Clin Invest] 2020 Apr 01; Vol. 130 (4), pp. 2024-2040.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Cytoskeleton*/genetics , Cytoskeleton*/metabolism , Genetic Therapy* , Nerve Regeneration* , Spinal Cord Injuries*/genetics , Spinal Cord Injuries*/metabolism , Spinal Cord Injuries*/therapy, Growth Cones/*metabolism , Sciatic Nerve/*physiology, Animals ; Dependovirus ; Mice ; Mice, Knockout ; Neuromuscular Junction/genetics ; Neuromuscular Junction/metabolism ; Profilins/biosynthesis ; Profilins/genetics ; Transduction, Genetic
مستخلص: After trauma, regeneration of adult CNS axons is abortive, causing devastating neurologic deficits. Despite progress in rehabilitative care, there is no effective treatment that stimulates axonal growth following injury. Using models with different regenerative capacities, followed by gain- and loss-of-function analysis, we identified profilin 1 (Pfn1) as a coordinator of actin and microtubules (MTs), powering axonal growth and regeneration. In growth cones, Pfn1 increased actin retrograde flow, MT growth speed, and invasion of filopodia by MTs, orchestrating cytoskeletal dynamics toward axonal growth. In vitro, active Pfn1 promoted MT growth in a formin-dependent manner, whereas localization of MTs to growth cone filopodia was facilitated by direct MT binding and interaction with formins. In vivo, Pfn1 ablation limited regeneration of growth-competent axons after sciatic nerve and spinal cord injury. Adeno-associated viral (AAV) delivery of constitutively active Pfn1 to rodents promoted axonal regeneration, neuromuscular junction maturation, and functional recovery of injured sciatic nerves, and increased the ability of regenerating axons to penetrate the inhibitory spinal cord glial scar. Thus, we identify Pfn1 as an important regulator of axonal regeneration and suggest that AAV-mediated delivery of constitutively active Pfn1, together with the identification of modulators of Pfn1 activity, should be considered to treat the injured nervous system.
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معلومات مُعتمدة: R01 AG050658 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: Cell Biology; Cytoskeleton; Neuroscience
المشرفين على المادة: 0 (Pfn1 protein, mouse)
0 (Profilins)
تواريخ الأحداث: Date Created: 20200117 Date Completed: 20201230 Latest Revision: 20201230
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7108904
DOI: 10.1172/JCI125771
PMID: 31945017
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI125771