Protein regulates structural plasticity of neurons
This study of mice with induced SPG8 showed them to have abnormal motor coordination with structural changes to dendrites and synapses found in cultured neurons. This impairment was corrected by restoring the strumpellin protein to normal levels, indicating that this protein regulates the structural plasticity of cortical neurons.
Abstract
Strumpellin/Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex subunit 5 (WASHC5) is a core component of the WASH complex, and its mutations confer pathogenicity for hereditary spastic paraplegia (HSP) type SPG8, a rare neurodegenerative gait disorder. WASH complex activates actin-related protein-2/3-mediated actin polymerization and plays a pivotal role in intracellular membrane trafficking in endosomes.
In this study, we examined the role of strumpellin in the regulation of structural plasticity of cortical neurons involved in gait coordination. Administration of a lentivirus containing a strumpellin-targeting short hairpin RNA (shRNA) to cortical motor neurons lead to abnormal motor coordination in mice. Strumpellin knockdown using shRNA attenuated dendritic arborization and synapse formation in cultured cortical neurons, and this effect was rescued by wild-type strumpellin expression. Compared with the wild-type, strumpellin mutants N471D or V626F identified in patients with SPG8 exhibited no differences in rescuing the defects. Moreover, the number of F-actin clusters in neuronal dendrites was decreased by strumpellin knockdown and rescued by strumpellin expression.
In conclusion, our results indicate that strumpellin regulates the structural plasticity of cortical neurons via actin polymerization.
SOURCE: Biochem Biophys Res Commun. 2023 Sep 17;673:169-174.
doi: 10.1016/j.bbrc.2023.06.071. Epub 2023 Jun 24. PMID: 37392480 Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Strumpellin/WASHC5 regulates the structural plasticity of cortical neurons involved in gait coordination
So-Hee Lim 1 , Sangyep Shin 2 , Na-Yoon Lee 3 , Sun Seek Min 2 , Nam-Soon Kim 1 , Da Yong Lee 4 , Jae-Ran Lee 5
1. Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea.
2. Department of Physiology and Biophysics, School of Medicine, Eulji University, Daejeon, 34824, South Korea.
3. Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea; Department of Bio-Molecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, South Korea.
4. Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea.
5. Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea.