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STIM1 is required for remodeling of the endoplasmic reticulum and microtubule cytoskeleton in steering growth cones


Pavez, M and Thompson, AC and Arnott, HJ and Mitchell, CB and D'Atri, I and Don, EK and Chilton, EK and Scott, EK and Lin, JY and Young, KM and Gasperini, RJ and Foa, L, STIM1 is required for remodeling of the endoplasmic reticulum and microtubule cytoskeleton in steering growth cones, Journal of Neuroscience, 39, (26) pp. 5095-5114. ISSN 0270-6474 (2019) [Refereed Article]

Copyright Statement

Copyright 2019 by the Society for Neuroscience

DOI: doi:10.1523/JNEUROSCI.2496-18.2019


The spatial and temporal regulation of calcium signaling in neuronal growth cones is essential for axon guidance. In growth cones, the endoplasmic reticulum (ER) is a significant source of calcium signals. However, it is not clear whether the ER is remodeled during motile events to localize calcium signals in steering growth cones. The expression of the ER-calcium sensor, stromal interacting molecule 1 (STIM1) is necessary for growth cone steering toward the calcium-dependent guidance cue BDNF, with STIM1 functioning to sustain calcium signals through store-operated calcium entry. However, STIM1 is also required for growth cone steering away from semaphorin-3a, a guidance cue that does not activate ER-calcium release, suggesting multiple functions of STIM1 within growth cones (Mitchell et al., 2012). STIM1 also interacts with microtubule plus-end binding proteins EB1/EB3 (Grigoriev et al., 2008). Here, we show that STIM1 associates with EB1/EB3 in growth cones and that STIM1 expression is critical for microtubule recruitment and subsequent ER remodeling to the motile side of steering growth cones. Furthermore, we extend our data in vivo, demonstrating that zSTIM1 is required for axon guidance in actively navigating zebrafish motor neurons, regulating calcium signaling and filopodial formation. These data demonstrate that, in response to multiple guidance cues, STIM1 couples microtubule organization and ER-derived calcium signals, thereby providing a mechanism where STIM1-mediated ER remodeling, particularly in filopodia, regulates spatiotemporal calcium signals during axon guidance.

Item Details

Item Type:Refereed Article
Keywords:axon guidance, calcium, endoplasmic reticulum, cell motility, microtubule, optogenetic, STIM1
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Pavez, M (Miss Macarena Pavez)
UTAS Author:Thompson, AC (Mr Adrian Thompson)
UTAS Author:Arnott, HJ (Mr Hayden Arnott)
UTAS Author:Mitchell, CB (Ms Camila Mitchell)
UTAS Author:Lin, JY (Dr John Lin)
UTAS Author:Young, KM (Professor Kaylene Young)
UTAS Author:Gasperini, RJ (Dr Rob Gasperini)
UTAS Author:Foa, L (Professor Lisa Foa)
ID Code:133862
Year Published:2019
Funding Support:National Health and Medical Research Council (1024145)
Web of Science® Times Cited:26
Deposited By:Medicine
Deposited On:2019-07-12
Last Modified:2022-08-23

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