Journal article
Tropomodulin’s Actin-Binding Abilities Are Required to Modulate Dendrite Development
Frontiers in molecular neuroscience, Vol.11, pp.357-357
10/09/2018
Handle:
https://hdl.handle.net/2376/106496
PMCID: PMC6190845
PMID: 30356860
Abstract
There are many unanswered questions about the roles of the actin pointed end capping and actin nucleation by tropomodulins (Tmod) in regulating neural morphology. Previous studies indicate that Tmod1 and Tmod2 regulate morphology of the dendritic arbor and spines. Tmod3, which is expressed in the brain, had only a minor influence on morphology. Although these studies established a defined role of Tmod in regulating dendritic and synaptic morphology, the mechanisms by which Tmods exert these effects are unknown. Here, we overexpressed a series of mutated forms of Tmod1 and Tmod2 with disrupted actin-binding sites in hippocampal neurons and found that Tmod1 and Tmod2 require both of their actin-binding sites to regulate dendritic morphology and dendritic spine shape. Proximity ligation assays (PLAs) indicate that these mutations impact the interaction of Tmod1 and Tmod2 with tropomyosins Tpm3.1 and Tpm3.2. This impact on Tmod/Tpm interaction may contribute to the morphological changes observed. Finally, we use molecular dynamics simulations (MDS) to characterize the structural changes, caused by mutations in the C-terminal helix of the leucine-rich repeat (LRR) domain of Tmod1 and Tmod2 alone and when bound onto actin monomers. Our results expand our understanding of how neurons utilize the different Tmod isoforms in development.
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Details
- Title
- Tropomodulin’s Actin-Binding Abilities Are Required to Modulate Dendrite Development
- Creators
- Kevin T Gray - Voiland School of Chemical Engineering and Bioengineering, Washington State UniversityHolly Stefen - Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South WalesThu N. A Ly - Voiland School of Chemical Engineering and Bioengineering, Washington State UniversityChristopher J Keller - Voiland School of Chemical Engineering and Bioengineering, Washington State UniversityMert Colpan - Voiland School of Chemical Engineering and Bioengineering, Washington State UniversityGary A Wayman - Integrative Physiology and Neuroscience, Washington State UniversityEdward Pate - Voiland School of Chemical Engineering and Bioengineering, Washington State UniversityThomas Fath - Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South WalesAlla S Kostyukova - Voiland School of Chemical Engineering and Bioengineering, Washington State University
- Publication Details
- Frontiers in molecular neuroscience, Vol.11, pp.357-357
- Academic Unit
- Integrative Physiology and Neuroscience, Department of; Chemical Engineering and Bioengineering, School of
- Publisher
- Frontiers Media S.A
- Identifiers
- 99900546543101842
- Language
- English
- Resource Type
- Journal article