The molecular basis for calcium-dependent axon pathfinding

Gómez, Timothy M.; Zheng, James

doi:10.1038/nrn1844

Cited by 293 publications

(288 citation statements)

References 126 publications

Supporting

Mentioning

279

Contrasting

Order By: Relevance

“…The asymmetric relocalization was also suppressed by application of the calcium chelator BAPTA-AM (Fig. 2D), emphasizing the role of Ca 2ϩ , a known messenger in GC gradient sensing (23) and in the signaling cascade of GABA (24). These results highlight the role of downstream components of the signaling pathway in the receptor reorganization and points to a cytoskeleton-driven redistribution of GABA A Rs.…”

Section: Resultsmentioning

confidence: 56%

“…We next investigated whether the relocalization of the membrane chemoreceptors (GABA A Rs) had implications on downstream intracellular signaling. We measured the concentration of intracellular calcium, an important factor in axon pathfinding (23) and in GABA signaling. At early stages of development of the nervous system, activation of GABA A Rs leads to membrane depolarization (28), which may trigger calcium entry through voltage-dependent calcium channels (23,24).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging

Bouzigues

Morel

Triller

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

129

146

View full text Add to dashboard Cite

During development of the nervous system, the tip of a growing axon, the growth cone (GC), must respond accurately to stimuli that direct its growth. This axonal navigation depends on extracellular concentration gradients of numerous guidance cues, including GABA. GCs can detect even weak directional signals, yet the mechanisms underlying this sensitivity remain unclear. Past studies in other eukaryotic chemotactic systems have pointed to the role of the spatial reorganization of the transduction pathway in their sensitive response. Here we have developed a singlemolecule assay to observe individual GABAA receptors (GABAARs) in the plasma membrane of nerve GCs subjected to directional stimuli. We report that in the presence of an external GABA gradient GABAARs redistribute asymmetrically across the GC toward the gradient source. Single-particle tracking of GABAARs shows that the redistribution results from transient interactions between the receptors and the microtubules. Moreover, the relocalization is accompanied by an enhancement in the asymmetry of intracellular calcium concentration. Altogether, our results reveal a microtubule-dependent polarized reorganization of chemoreceptors at the cell surface and suggest that this polarization serves as an amplification step in GABA gradient sensing by nerve GCs.axonal guidance ͉ chemotaxis ͉ single molecule ͉ polarity

show abstract

Section: Resultsmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging

Bouzigues

Morel

Triller

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

129

146

View full text Add to dashboard Cite

show abstract

“…Calcium is a ubiquitous signal that participates in different processes and cell domains during cell migration (Gomez and Zheng, 2006;Zheng and Poo, 2007). This has been demonstrated in migrating fibroblasts that keep a rear-to-front calcium gradient in addition to local and short-lived high-calcium microdomains which are most active at the leading lamella (Wei et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

Martini

Valdeolmillos²

2010

Journal of Neuroscience

111

134

View full text Add to dashboard Cite

Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules.

show abstract

“…However, the influence of calcium on events associated with neuronal development is very much context dependent as changes in intracellular calcium can elicit negative or positive responses depending on the route of entry, concentration of calcium at the time of change, or size of the calcium gradient (Gomez and Zheng 2006). Further, even the type of channel through which calcium may enter the neuron can differentially influence neurite growth and branching (Heng et al 1999).…”

Section: Calcium and Neuronal Maturationmentioning

confidence: 99%

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

et al. 2008

View full text Add to dashboard Cite

It has become increasingly clear that agents that disrupt calcium homeostasis may also be toxic to developing neurons. Using isolated primary neurons, we sought to understand the neurotoxicity of agents such as MK801 (which blocks ligand-gated calcium entry), BAPTA (which chelates intracellular calcium), and thapsigargin (TG; which inhibits the endoplasmic reticulum Ca 2+ -ATPase pump). Thus, E18 at cotical neuons wee grown for 1 day in vitro (DIV) and then exposed to vehicle (0.1% DMSO), MK801 (0.01-20 μM), BAPTA (0.1-20 μM), or TG (0.001-1 μM) for 24 h. We found that all three agents could profoundly influence early neuronal maturation (growth cone expansion, neurite length, neurite complexity), with the order of potency being MK801 < BAPTA < TG. We next asked if cultures exposed to these agents were able to re-establish their developmental program once the agent was removed. When we examined network maturity at 4 and 7 DIV, the order of recovery was MK801 > BAPTA > TG. Thus, mechanistically distinct ways of disrupting calcium homeostasis differentially influenced both short-term and long-term neuronal maturation. These observations suggest that agents that act by altering intracellular calcium and are used in obstetrics or neonatology may be quite harmful to the still-developing human brain.

show abstract

The molecular basis for calcium-dependent axon pathfinding

Cited by 293 publications

References 126 publications

Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging

Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

Contact Info

Product

Resources

About