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Homer regulates calcium signalling in growth cone turning

Citation

Gasperini, RJ and Choi-Lundberg, DL and Thompson, MJW and Mitchell, CB and Foa, LC, Homer regulates calcium signalling in growth cone turning, Neural Development, 4, (1) pp. 1-19. ISSN 1749-8104 (2009) [Refereed Article]


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Copyright Statement

2009 Gasperini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Official URL: http://www.neuraldevelopment.com/content/4/1/29

DOI: doi:10.1186/1749-8104-4-29

Abstract

Background: Homer proteins are post-synaptic density proteins with known functions in receptor trafficking and calcium homeostasis. While they are key mediators of synaptic plasticity, they are also known to function in axon guidance, albeit by mechanisms that are yet to be elucidated. Homer proteins couple extracellular receptors such as metabotropic glutamate receptors and the transient receptor potential canonical family of cation channels to intracellular receptors such as inositol triphosphate and ryanodine receptors on intracellular calcium stores and, therefore, are well placed to regulate calcium dynamics within the neural growth cone. Here we used growth cones from dorsal root ganglia, a well established model in the field of axon guidance, and a growth cone turning assay to examine Homer1 function in axon guidance. Results: Homer1 knockdown reversed growth cone turning from attraction to repulsion in response to the calcium-dependent guidance cues brain derived neurotrophic factor and netrin-1. Conversely, Homer1 knockdown had no effect on repulsion to the calcium-independent guidance cue Semaphorin-3A. This reversal of attractive turning suggested a requirement for Homer1 in a molecular switch. Pharmacological experiments confirmed that the operational state of a calciumcalmodulin dependent protein kinase II/calcineurin phosphatase molecular switch was dependent on Homer1 expression. Calcium imaging of motile growth cones revealed that Homer1 is required for guidance-cue-induced rise of cytosolic calcium and the attenuation of spontaneous cytosolic calcium transients. Homer1 knockdown-induced calcium transients and turning were inhibited by antagonists of store-operated channels. In addition, immunocytochemistry revealed the close association of Homer1 with the store-operated proteins TRPC1 and STIM1 within dorsal root ganglia growth cones. Conclusion: These experiments provide evidence that Homer1 is an essential component of the calcium signalling repertoire within motile growth cones, regulating guidance-cue-induced calcium release and maintaining basal cytosolic calcium.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Gasperini, RJ (Dr Rob Gasperini)
Author:Choi-Lundberg, DL (Dr Derek Choi-Lundberg)
Author:Thompson, MJW (Dr Michael Thompson)
Author:Mitchell, CB (Miss Camilla Mitchell)
Author:Foa, LC (Professor Lisa Foa)
ID Code:61380
Year Published:2009
Web of Science® Times Cited:22
Deposited By:Medicine
Deposited On:2010-03-03
Last Modified:2012-04-20
Downloads:389 View Download Statistics

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