Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse Formation

• Type of Material: Article
• Authors: Omotola F. Omotade, Emory University; Yanfang Rui, Emory University; Wenliang Lei, Emory University; Kuai Yu, Emory University; Criss Hartzell Jr., Emory University; Velia M. Fowler, Scripps Research Institute; James Zheng, Emory University
• Language: English
• Date: 2018-11-28
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: © 2018 the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.3325-17.2018
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 38
• Issue: 48
• Start Page: 10271
• End Page: 10285
• Grant/Funding Information: This research project was supported in part by research grants from the National Institutes of Health to J.Q.Z. (GM-083889, MH-104632, and MH-108025), O.F.O. (5F31-NS-092437-03), V.M.F. (EY-017724), and H.C.H. (EY-014852 and AR-067786); as well as by Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience National Institute of Neurological Disorders and Stroke Core Facilities Grant 5P30-NS-055077.
• Keywords: TROPOMYOSIN; EXPRESSION; SPECTRIN; Science & Technology; dendritic arborization; Neurosciences; ORGANIZATION; ACTIN; SUBCORTICAL CYTOSKELETON PERIODICITY; pointed end; actin; cytoskeleton; dendritic spines; STED NANOSCOPY; SPINES; Life Sciences & Biomedicine; DYNAMICS; SYNAPTOGENESIS; Neurosciences & Neurology
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

Neurons of the CNS elaborate highly branched dendritic arbors that host numerous dendritic spines, which serve as the postsynaptic platform for most excitatory synapses. The actin cytoskeleton plays an important role in dendrite development and spine formation, but the underlying mechanisms remain incompletely understood. Tropomodulins (Tmods) are a family of actin-binding proteins that cap the slow-growing (pointed) end of actin filaments, thereby regulating the stability, length, and architecture of complex actin networks in diverse cell types. Three members of the Tmod family, Tmod1, Tmod2, and Tmod3 are expressed in the vertebrate CNS, but their function in neuronal development is largely unknown. In this study, we present evidence that Tmod1 and Tmod2 exhibit distinct roles in regulating spine development and dendritic arborization, respectively. Using rat hippocampal tissues from both sexes, we find that Tmod1 and Tmod2 are expressed with distinct developmental profiles: Tmod2 is expressed early during hippocampal development, whereas Tmod1 expression coincides with synaptogenesis. We then show that knockdown of Tmod2, but not Tmod1, severely impairs dendritic branching. Both Tmod1 and Tmod2 are localized to a distinct subspine region where they regulate local F-actin stability. However, the knockdown of Tmod1, but not Tmod2, disrupts spine morphogenesis and impairs synapse formation. Collectively, these findings demonstrate that regulation of the actin cytoskeleton by different members of the Tmod family plays an important role in distinct aspects of dendrite and spine development.