Highwire Regulates Presynaptic BMP Signaling Essential for Synaptic Growth

McCabe, Brian D.; Hom, Sabrina; Aberle, Hermann; Fetter, Richard D.; Marqués, Guillermo; Haerry, Theodore E; Wan, Hong; O’Connor, Michael B.; Goodman, Corey S.; Haghighi, A. Pejmun

doi:10.1016/s0896-6273(04)00073-x

Cited by 212 publications

(264 citation statements)

References 69 publications

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“…Chimeric receptors containing elements from both Wit and Sax were nonfunctional. Similar results have recently been obtained at the NMJ by McCabe et al (2004) that serve to underline the fact that although Sax is seemingly required for correct NMJ development, it is not sufficient to transmit the Wit signal. In the absence of sax, NMJs exhibit reductions in both synaptic size and neurotransmission, a phenotype that is, somewhat perplexingly, recapitulated by pan-neuronal expression of DNtkv but not by DNsax (Rawson et al, 2003;McCabe et al, 2004).…”

Section: Discussionsupporting

confidence: 83%

“…Similar results have recently been obtained at the NMJ by McCabe et al (2004) that serve to underline the fact that although Sax is seemingly required for correct NMJ development, it is not sufficient to transmit the Wit signal. In the absence of sax, NMJs exhibit reductions in both synaptic size and neurotransmission, a phenotype that is, somewhat perplexingly, recapitulated by pan-neuronal expression of DNtkv but not by DNsax (Rawson et al, 2003;McCabe et al, 2004). Thus, although there are details that remain to be clarified, clearly BMP signaling at the Moreover, postsynaptic expression of rut, which is normally sufficient to significantly increase evoked synaptic currents in aCC/RP2 (Fig.…”

Section: Discussionsupporting

confidence: 83%

“…At the NMJ, BMP signaling is seemingly mediated through Wit-dependent phosphorylation of R-Smads in the presynaptic motoneurons (Marqués et al, 2002;McCabe et al, 2003McCabe et al, , 2004Rawson et al, 2003). These studies failed, however, to show P-Mad reactivity in central interneurons which, in the light of the present findings, might be indicative of differing transduction mechanisms centrally compared with peripherally.…”

Section: Discussioncontrasting

confidence: 73%

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Synaptic Strengthening Mediated by Bone Morphogenetic Protein-Dependent Retrograde Signaling in theDrosophilaCNS

Baines¹

2004

J. Neurosci.

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Retrograde signaling is an essential component of synaptic development and physiology. Previous studies show that bone morphogenetic protein (BMP)-dependent retrograde signaling is required for the proper development of the neuromuscular junction (NMJ) in Drosophila. These studies, moreover, raised the significant possibility that the development of central motor circuitry might similarly be reliant on such signaling. To test this hypothesis, retrograde signaling between postsynaptic motoneurons and their presynaptic interneurons is examined. Postsynaptic expression of an adenylate cyclase encoded by rutabaga (rut), is sufficient to strengthen synaptic transmission at these identified central synapses. Results are presented to show that the underlying mechanism is dependent on BMP retrograde signaling. Thus, presynaptic expression of an activated TGF-␤ receptor, thickvien (tkv), or postsynaptic expression of a TGF-␤ ligand, glass-bottom boat ( gbb), is sufficient to phenocopy strengthening of synaptic transmission. In the absence of gbb, endogenous synaptic transmission is significantly weakened and, moreover, postsynaptic overexpression of rut is unable to potentiate synaptic function. Potentiation of presynaptic neurotransmitter release, mediated by increased postsynaptic expression of gbb, is dependent on normal cholinergic activity, indicative that either the secretion of this retrograde signal, or its transduction, is activity dependent. Thus, in addition to the development of the NMJ and expression of myoactive FMRFamide-like peptides in specific central neurons, the results of the present study indicate that this retrograde signaling cascade also integrates the development and function of central motor circuitry that controls movement in Drosophila larvae.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 83%

Section: Discussioncontrasting

confidence: 73%

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Synaptic Strengthening Mediated by Bone Morphogenetic Protein-Dependent Retrograde Signaling in theDrosophilaCNS

Baines¹

2004

J. Neurosci.

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“…In addition, wild type Smad4 can be mono-ubiquitinated by yet unidentified E3 ligases or sumoylated by Ubc9 and PIAS family E3 ligases (19 -26). In Drosophila, the E3 ligase Highwire down-regulates the Co-Smad, Medea (27). Both mono-ubiquitination and sumoylation of Smad4 lead to stabilization of the protein and enhanced TGF-␤ signaling.…”

mentioning

confidence: 99%

Degradation of the Tumor Suppressor Smad4 by WW and HECT Domain Ubiquitin Ligases

Morén

Imamura

Miyazono

et al. 2005

Journal of Biological Chemistry

175

141

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“…Several membrane or secretory proteins and their receptors are candidate molecules that might contribute to the formation of specific synapses (Wells et al, 1999;Tao and Poo, 2001;Lee et al, 2003;Blagburn and Bacon, 2004;Graf et al, 2004;McCabe et al, 2004;Shen et al, 2004;Boucard et al, 2005: Chih et al, 2005Christopherson et al, 2005;Sara et al, 2005;Wang et al, 2007). However, the orchestration of the signaling mechanisms mediating target selection, branching, synapse formation, and maintenance is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Role of Protein Kinase C in Regulating the Formation and Maturation of Specific Synapses

Hu¹,

Chen²,

Schacher³

2007

J. Neurosci.

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Target-dependent increases in axon growth and varicosities accompany the formation of functional synapses between Aplysia sensory neurons and specific postsynaptic neurons (L7 and not L11). The enhanced growth is regulated in part by a target-dependent increase in the secretion of sensorin, the sensory neuron neuropeptide. We report here that protein kinase C (PKC) activity is required for synapse formation by sensory neurons with L7 and for the target-dependent increases in sensorin synthesis and secretion. Blocking PKC activity reversibly blocked synapse formation and axon growth of sensory neurons contacting L7, but did not affect axon growth of sensory neurons contacting L11 or axon growth of the postsynaptic targets. Blocking PKC activity also blocked the target-induced increase in sensorin synthesis and secretion. Sensorin then activates additional signaling pathways required for synapse maturation and synapseassociated growth. Exogenous anti-sensorin antibody blocked target-induced activation and translocation into sensory neuron nuclei of p42/44 mitogen-activated protein kinase (MAPK), attenuated synapse maturation, and curtailed growth of sensory neurons contacting L7, but not the growth of sensory neurons contacting L11. Inhibitors of MAPK or phosphoinositide 3-kinase also attenuated synapse maturation and curtailed growth and varicosity formation of sensory neurons contacting L7, but not growth of sensory neurons contacting L11. These results suggest that PKC activity regulated by specific cell-cell interactions initiates the formation of specific synapses and the subsequent synthesis and release of a neuropeptide to activate additional signaling pathways required for synapse maturation.

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Highwire Regulates Presynaptic BMP Signaling Essential for Synaptic Growth

Cited by 212 publications

References 69 publications

Synaptic Strengthening Mediated by Bone Morphogenetic Protein-Dependent Retrograde Signaling in theDrosophilaCNS

Synaptic Strengthening Mediated by Bone Morphogenetic Protein-Dependent Retrograde Signaling in theDrosophilaCNS

Degradation of the Tumor Suppressor Smad4 by WW and HECT Domain Ubiquitin Ligases

Multifunctional Role of Protein Kinase C in Regulating the Formation and Maturation of Specific Synapses

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