Axon Response to Guidance Cues Is Stimulated by Acetylcholine in <i>Caenorhabditis elegans</i>

Xu, Yan; Ren, Xingcong; Quinn, Christopher C.; Wadsworth, William G.

doi:10.1534/genetics.111.133546

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…Previous work has demonstrated the V-type ATPases are also associated with neurotransmitter loading in synaptic vesicle [52, 53]. Due to the P7 stage of development to be highly associated with axonal and dendritic proliferation [54] with dendritic formation and synaptic strength dependent on signaling [55–60], the increase in the V-type ATPases observed is likely also associated with increased synaptic signaling. These results suggest there is increased mitochondrial trafficking to the synapses and increased mitophagy occurring at the P7 stage of brain development.…”

Section: Discussionmentioning

confidence: 93%

Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands

Villeneuve

Stauch

Fox

2014

Journal of Proteomics

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Many biological processes converge on the mitochondria. In such systems, where many pathways converge, manipulation of the components can produce varied and far-reaching effects. Due to the centrality of the mitochondria in many cellular pathways, we decided to investigate the brain mitochondrial proteome during early development. Using a SWATH mass spectrometry-based technique, we were able to identify vast proteomic alterations between whole brain mitochondria from rats at embryonic day 18 compared to postnatal day 7. These findings include statistically significant alterations in proteins involved in glycolysis and mitochondrial trafficking/dynamics. Additionally, bioinformatic analysis enabled the identification of HIF1A and XBP1 as upstream transcriptional regulators of many of the differentially expressed proteins. These data suggest that the cell is rearranging mitochondria to accommodate special energy demands and that cytosolic proteins exert mitochondrial effects through dynamic interactions with mitochondria.

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Section: Discussionmentioning

confidence: 93%

Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands

Villeneuve

Stauch

Fox

2014

Journal of Proteomics

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“…Axon guidance was analyzed as described previously [ 51 , 52 ]. The zdIs13 transgene [ 53 ], which expresses Ptph-1::gfp, was used to visualize the HSN axon in young adult animals.…”

Section: Methodsmentioning

confidence: 99%

SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) Function Interdependently to Promote Axon Guidance by Regulating the MIG-2 GTPase

Taru

Jin³

et al. 2015

PLoS Genet

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During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling. Here, we show that UNC-40, SAX-3 and the SYD-1 RhoGAP-like protein function interdependently to regulate the MIG-2 (Rac) GTPase in the HSN axon of C. elegans. We find that SYD-1 mediates an UNC-6 (netrin) independent UNC-40 activity to promote ventral axon guidance. Genetic analysis suggests that SYD-1 function in axon guidance requires both UNC-40 and SAX-3 activity. Moreover, the cytoplasmic domains of UNC-40 and SAX-3 bind to SYD-1 and SYD-1 binds to and negatively regulates the MIG-2 (Rac) GTPase. We also find that the function of SYD-1 in axon guidance is mediated by its phylogenetically conserved C isoform, indicating that the role of SYD-1 in guidance is distinct from its previously described roles in synaptogenesis and axonal specification. Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals.

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“…The PCR product was cut with NheI and KpnI and ligated into the Nhe1 and Kpn1 sites of pIM207 [17], [44].…”

Section: Methodsmentioning

confidence: 99%

MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways

Xu¹,

Quinn

2012

PLoS Genet

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Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone. A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 (lamellipodin). MIG-10 is thought to asymmetrically promote outgrowth by inducing actin polymerization. However, the mechanism that links MIG-10 to actin polymerization is not known. We have identified the actin regulatory protein ABI-1 as a partner for MIG-10 that can mediate its outgrowth-promoting activity. The SH3 domain of ABI-1 binds to MIG-10, and loss of function of either of these proteins causes similar axon guidance defects. Like MIG-10, ABI-1 functions in both the attractive UNC-6 (netrin) pathway and the repulsive SLT-1 (slit) pathway. Dosage sensitive genetic interactions indicate that MIG-10 functions with ABI-1 and WVE-1 to mediate axon guidance. Epistasis analysis reveals that ABI-1 and WVE-1 function downstream of MIG-10 to mediate its outgrowth-promoting activity. Moreover, experiments with cultured mammalian cells suggest that the interaction between MIG-10 and ABI-1 mediates a conserved mechanism that promotes formation of lamellipodia. Together, these observations suggest that MIG-10 interacts with ABI-1 and WVE-1 to mediate the UNC-6 and SLT-1 guidance pathways.

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Axon Response to Guidance Cues Is Stimulated by Acetylcholine in Caenorhabditis elegans

Cited by 5 publications

References 42 publications

Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands

Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands

SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) Function Interdependently to Promote Axon Guidance by Regulating the MIG-2 GTPase

MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways

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