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STIM1 is required for remodeling of the endoplasmic reticulum and microtubule cytoskeleton in steering growth cones
journal contribution
posted on 2023-05-20, 05:33 authored by Pavez, M, Thompson, AC, Hayden ArnottHayden Arnott, Mitchell, CB, D'Atri, I, Don, EK, Chilton, EK, Scott, EK, John LinJohn Lin, Kaylene YoungKaylene Young, Robert GasperiniRobert Gasperini, Lisa FoaLisa FoaThe 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.
Funding
National Health & Medical Research Council
History
Publication title
Journal of NeuroscienceVolume
39Issue
26Pagination
5095-5114ISSN
0270-6474Department/School
Tasmanian School of MedicinePublisher
Society for NeurosciencePlace of publication
11 Dupont Circle, Nw, Ste 500, Washington, USA, Dc, 20036Rights statement
Copyright 2019 by the Society for NeuroscienceRepository Status
- Restricted