STIM1 Is Required for Remodeling of the Endoplasmic Reticulum and Microtubule Cytoskeleton in Steering Growth Cones

Pavez, Macarena; Thompson, Adrian C.; Arnott, Hayden J.; Mitchell, Camilla B.; D’Atri, Ilaria; Don, Emily K.; Chilton, John K.; Scott, Ethan K.; Lin, John Y.; Young, Karen; Gasperini, Robert; Foa, Lisa

doi:10.1523/jneurosci.2496-18.2019

Cited by 45 publications

(37 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possibility is that microtubules deliver components necessary for stabilization of adhesion complexes (Kaverina et al, 2002). Another possibility is that microtubule entry promotes advance of smooth endoplasmic reticulum (SER) and that interaction with the adhesion complex stabilizes both the dynamic microtubules and the SER (Dailey and Bridgman, 1989; Pavez et al, 2019; Zhang and Forscher, 2009). These possibilities are not mutually exclusive.…”

Section: Discussionmentioning

confidence: 99%

“…However, microtubule dynamics also correlate with growth cone movement (Sabry et al, 1991; Tanaka and Kirschner, 1991), initial neuronal polarization (Witte et al, 2008) and are required for turning (Buck and Zheng, 2002). Bulk advance of microtubules correlates with neurite elongation (Athamneh et al, 2017) and microtubule associated proteins have been implicated in steering (Pavez et al, 2019). In addition, it has been shown that microtubules or microtubule-based motors can be manipulated to influence turning even when actin dynamics are unperturbed (Challacombe et al, 1997) (Buck and Zheng, 2002; Kahn and Baas, 2016; Nadar et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variation and Selection in Axon Navigation Through Microtubule-Dependent Stepwise Growth Cone Advance

Turney

Chandrasekar²,

Ahmed³

et al. 2020

Preprint

View full text Add to dashboard Cite

24Myosin II (MII) activity is required for elongating mammalian sensory axons to change speed 25 and direction in response to Nerve Growth Factor (NGF) and laminin-1 (LN). NGF signaling 26 induces faster outgrowth on LN through regulation of actomyosin restraint of microtubule 27 advance into the growth cone periphery. It remains unclear whether growth cone turning on LN 28 works through the same mechanism and, if it does, how the mechanism produces directed 29 advance. Using a novel method for substrate patterning, we tested how directed advance 30 occurs on LN by creating a gap immediately in front of a growth cone advancing on a narrow 31 LN path. The growth cone stopped until an actin-rich protrusion extended over the gap, 32 adhered to LN, and became stabilized. Stepwise advance over the gap was triggered by 33 microtubule +tip entry up to the adhesion site of the protrusion and was independent of traction 34 force pulling. We found that the probability of microtubule entry is regulated at the level of the 35 individual protrusion and is sensitive to the rate of microtubule polymerization and the rate of 36 rearward actin flow as controlled by adhesion-cytoskeletal coupling and MII. We conclude that 37 growth cone navigation is an iterative process of variation and selection. Growth cones extend 38 leading edge actin-rich protrusions that adhere transiently (variation). Microtubule entry up to 39 an adhesion site stabilizes a protrusion (selection) leading to engorgement, consolidation, 40 protrusive activity distal to the adhesion site, and stepwise growth cone advance. The 41 orientation of the protrusion determines the direction of advance. 42 87 5 preference for LN primarily through traction force pulling supporting the prevailing view that 88 substrate coupling is instructive (necessary and sufficient) for advance during directed growth 89 and that the main function of MII is to develop pulling forces via the adhesion sites. However, if 90 MII inhibition does not block advance then the core mechanism may be regulation of 91 actomyosin restraint of microtubule advance as we recently proposed (Turney et al., 2016). 92Here we test between these possibilities. 93 94 RESULTS 95 96 Novel assay for analysis of stepwise growth cone advance 97 Mouse dorsal root ganglion (DRG) or superior cervical ganglion (SCG) neurons were cultured 98 in a microfluidic Campenot chamber that served to hinder migration of glia into the axon 99 compartment and to chemically isolate distal axon segments and growth cones from cell 100 bodies. Axons exiting the channels of the chamber (10 µm wide) grew onto narrow LN lanes 101 (9-12 µm wide). On many lanes we produced gaps (non-adhesive regions) over which axons 102 had to cross for the elongation to continue. Both the lanes and the gaps were created by a new 103 method of substrate patterning (Live Cell Substrate Patterning or LSCP; see Experimental 104 Procedures) which uses region of interest (ROI) scanning of intense multiphoton laser light to 105 remove PLO, FN and LN f...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variation and Selection in Axon Navigation Through Microtubule-Dependent Stepwise Growth Cone Advance

Turney

Chandrasekar²,

Ahmed³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Regulation of ER-Ca 2+ release channels KD: decreased axonal length (Tsai et al, 2015) LOF: impaired anterograde transport (Tsai et al, 2015) AD (Mishina et al, 2008;Hedskog et al, 2013) ALS (Al-Saif et al, 2011;Prause et al, 2013) Chemotherapy-induced peripheral neuropathy (Bruna and Velasco, 2018) HD (Hyrskyluoto et al, 2013;Miki et al, 2015;Ryskamp et al, 2017) PD (Mishina et al, 2005;Mori et al, 2012) Spinal CMT (Li et al, 2015) spastin ER-Endosomes tethering MT severing LDs growth regulation KD: impaired axon outgrowth (Wood et al, 2006); reduced presynaptic area, increased excitatory junction potential amplitude, and accumulation of stabilized MTs (Trotta et al, 2004); loss of LDs (Papadopoulos et al, 2015); enhanced endosomal tubulation (Allison et al, 2013) LOF: reduced axonal length (Solowska et al, 2008); impaired regeneration (Stone et al, 2012); decreased presynaptic terminals size, decreased quantal content, and presynaptic loss of stabile MTs (Sherwood et al, 2004); large lysosomes (Allison et al, 2017) OE: reduced excitatory junction potential amplitude and presynaptic loss of stabile MTs (Trotta et al, 2004); increased LDs size and number (Papadopoulos et al, 2015) HSP (Hazan et al, 1999) STIM1 ER-PM tethering Regulation of ER-Ca 2+ uptake ER-MTs interaction KD: impaired presynaptic Ca 2+ influx and exocytosis (de Juan-Sanz et al, 2017) LOF/OE: impaired axon guidance (Shim et al, 2013) LOF: reduced ER translocation into growth cone filopodia (Pavez et al, 2019) AD (Gutierrez-Merino et al, 2018)…”

Section: Sigr1mentioning

confidence: 99%

“…In TACs, the tip of an ER tubule is attached to the tip of a MT plus end, through a complex containing the ER protein STIM1 and the MT-associated protein EB1. This binding leads to the ER tubule movement when the MT grows or retracts (Grigoriev et al, 2008;Pavez et al, 2019). The other mechanism mediating ER tubule movement along MTs, faster and more frequent than TAC, is ER sliding, driven by MT motor proteins such as kinesin-1 and dynein (Woźniak et al, 2009).…”

Section: Mt-mediated Tubular Er Dynamicsmentioning

confidence: 99%

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

2020

View full text Add to dashboard Cite

The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca 2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca 2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.

show abstract

“…Tse et al reported that SOCE-like activity in neurons derived from dissociated neurospheres of zebrafish [ 48 ]. Zebrafish Stim1 was shown to be crucial for the axon guidance of motor neurons and the regulation of calcium signaling [ 49 ]. We recently showed that the knockout of one orthologue of Stim2 , stim2b , caused hyperactivity and increased the susceptibility to seizures in zebrafish larvae [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Knockout of stim2a Increases Calcium Oscillations in Neurons and Induces Hyperactive-Like Phenotype in Zebrafish Larvae

Gupta

Wasilewska

Palchevska

et al. 2020

IJMS

View full text Add to dashboard Cite

Stromal interaction molecule (STIM) proteins play a crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca2+ sensors. In neurons, STIM2 was shown to have distinct functions from STIM1. However, its role in brain activity and behavior was not fully elucidated. The present study analyzed behavior in zebrafish (Danio rerio) that lacked stim2a. The mutant animals had no morphological abnormalities and were fertile. RNA-sequencing revealed alterations of the expression of transcription factor genes and several members of the calcium toolkit. Neuronal Ca2+ activity was measured in vivo in neurons that expressed the GCaMP5G sensor. Optic tectum neurons in stim2a−/− fish had more frequent Ca2+ signal oscillations compared with neurons in wildtype (WT) fish. We detected an increase in activity during the visual–motor response test, an increase in thigmotaxis in the open field test, and the disruption of phototaxis in the dark/light preference test in stim2a−/− mutants compared with WT. Both groups of animals reacted to glutamate and pentylenetetrazol with an increase in activity during the visual–motor response test, with no major differences between groups. Altogether, our results suggest that the hyperactive-like phenotype of stim2a−/− mutant zebrafish is caused by the dysregulation of Ca2+ homeostasis and signaling.

show abstract

STIM1 Is Required for Remodeling of the Endoplasmic Reticulum and Microtubule Cytoskeleton in Steering Growth Cones

Cited by 45 publications

References 100 publications

Variation and Selection in Axon Navigation Through Microtubule-Dependent Stepwise Growth Cone Advance

Variation and Selection in Axon Navigation Through Microtubule-Dependent Stepwise Growth Cone Advance

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

Knockout of stim2a Increases Calcium Oscillations in Neurons and Induces Hyperactive-Like Phenotype in Zebrafish Larvae

Contact Info

Product

Resources

About