ArticleMolecular and cellular neurosciences2013
HspB1 silences translation of PDZ-RhoGEF by enhancing miR-20a and miR-128 expression to promote neurite extension.
Article in Molecular and cellular neurosciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Review
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- STAU1 selectively regulates the expression of inflammatory and immune response genes and alternative splicing of the nerve growth factor receptor signaling pathway.Oncology reports · 2020Article
- miR-30b Promotes spinal cord sensory function recovery via the Sema3A/NRP-1/PlexinA1/RhoA/ROCK Pathway.Journal of cellular and molecular medicine · 2020Article
- Silencing miR-20a-5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa-RhoA-mediated synaptic plasticity.Journal of cellular and molecular medicine · 2020Article
- Biomechanical Forces Regulate Gene Transcription During Stretch-Mediated Growth of Mammalian Neurons.Frontiers in neuroscience · 2020Article
- Extracellular RNAs as Biomarkers of Sporadic Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases.International journal of molecular sciences · 2019Review
- Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.Autophagy · 2019Article
- Targeting Axon Integrity to Prevent Chemotherapy-Induced Peripheral Neuropathy.Molecular neurobiology · 2019Article
- Distal Axonal Proteins and Their Related MiRNAs in Cultured Cortical Neurons.Molecular neurobiology · 2019Article
- MiR-20a Plays a Key Regulatory Role in the Repair of Spinal Cord Dorsal Column Lesion via PDZ-RhoGEF/RhoA/GAP43 Axis in Rat.Cellular and molecular neurobiology · 2019Article
- MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies.Aging cell · 2018Review
- Heat Shock Proteins Regulatory Role in Neurodevelopment.Frontiers in neuroscience · 2018Review
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4 authors at 3 institutions in 1 country.
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Abstract
HspB1 is a small heat shock protein implicated in neuronal survival and neurite growth; mutations in HspB1 have been identified in hereditary motor neuronopathies and Charcot Marie Tooth Type 2 neuropathies. In cortical neurons we found that expression of HspB1 decreased RhoA activity and RhoA-GTP protein, and reversed the inhibition of neurite extension induced by NogoA. HspB1 decreased PDZ-RhoGEF, a RhoA specific guanine nucleotide exchange factor, while other regulators of RhoA activity were unchanged. The decrease in PDZ-RhoGEF was independent of proteasomal or lysosomal degradation pathways and was not associated with changes in PDZ-RhoGEF mRNA. We sequenced the 3'UTR of rat PDZ-RhoGEF and found binding sites for miRNAs miR-20a, miR-128 and miR-132. Expression of these microRNAs was substantially increased in cortical neurons transfected with HspB1. Co-transfection of HspB1 with specific inhibitors of miR-20a or miR-128 prevented the decrease in PDZ-RhoGEF and blocked the neurite growth promoting effects of HspB1. Using the 3'UTR of PDZ-RhoGEF mRNA in a luciferase reporter construct we observed that HspB1, miR-20a and miR-128 each inhibited luciferase expression. We conclude that HspB1 regulates RhoA activity through modulation of PDZ-RhoGEF levels achieved by translational control through enhanced expression of specific miRNAs (miR-20a and miR-128). Regulation of RhoA activity by translational silencing of PDZ-RhoGEF may be the mechanism through which HspB1 is involved in regulation of neurite growth. As RhoA-GTPase plays a regulatory role in the organization and stability of cytoskeletal networks through its downstream effectors, the results suggest a possible mechanism linking HspB1 mutations and axonal cytoskeletal pathology.
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