Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor

Corset, Véronique; Nguyen-Ba-Charvet, Kim T.; Forcet, Christelle; Moyse, Emmanuel; Chédotal, Alain; Mehlen, Patrick

doi:10.1038/35037600

Cited by 197 publications

(158 citation statements)

References 22 publications

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“…In addition, the membraneassociated, G-protein-coupled adenosine A2b receptor functions as a netrin-1 receptor. However, it is unclear whether the A2b receptor is involved in netrin-1-mediated axon-guidance signaling [29][30][31] . In epithelial cells, binding of the netrin-1 C-terminus with integrins α3β1 and α6β4 provides cues for axon adhesion and migration [32] .…”

Section: Receptorsmentioning

confidence: 99%

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

Ding

Liao

2014

Neurosci. Bull.

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Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light of this, researchers have been actively searching for methods to treat cerebral infarction. Netrins were fi rst identifi ed as a family of proteins that mediate axon guidance and direct axon migration during embryogenesis. Later studies have revealed other functions of this protein family. In this review, we focus on netrin-1, which has been shown to be involved in axon migration and angiogenesis, which are required for recovery after cerebral ischemia. Thus, therapies targeting netrin-1 may be useful for the treatment of ischemic stroke.

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Section: Receptorsmentioning

confidence: 99%

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

Ding

Liao

2014

Neurosci. Bull.

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“…In the adult mouse brain, netrin-1 is expressed by some neurons and myelinating oligodendrocytes. 141 In neurons, netrin-1 has several known receptors (Figure 4), Deleted in colorectal cancer (DCC), UNC5A, UNC5B, UNC5C and UNC5D 142,143 and the adenosine receptor A2b.17, 144,145 (see Patel and Van Vactor 146 for a review). In neurons, DCC was shown to mediate the attractive activity of netrin-1, in association with A2b.…”

Section: Netrins and Their Receptorsmentioning

confidence: 99%

“…In neurons, DCC was shown to mediate the attractive activity of netrin-1, in association with A2b. 144,145 UNC5s seem required for netrin-1 repulsive activity, at least in vitro [147][148][149] and this might also require interaction with DCC. 140,150 However, in C. elegans and Drosophila embryo 150 UNC5 could signal independently of DCC.…”

Section: Netrins and Their Receptorsmentioning

confidence: 99%

The brain within the tumor: new roles for axon guidance molecules in cancers

2005

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Slits, semaphorins and netrins are three families of proteins that can attract or repel growing axons and migrating neurons in the developing nervous system of vertebrates and invertebrates. Recent studies have shown that they are widely expressed outside the nervous system and that they may play important roles in cancers. Several of the genes encoding these proteins are localized on chromosomal region associated with frequent loss-of-heterozygosity in tumors and cancer cell lines and there is also significant hypermethylation of their promoter suggesting that they may act as tumor suppressors. In addition, proteins in all these families and their receptors appear to control the vascularization of the tumors. Last, many axon guidance molecules also regulate cell migration and apoptosis in normal and tumorigenic tissues. Overall, this suggests that molecules that could mimick or block the activity of axon guidance molecules may be used as therapeutic agents for the treatment of malignancy.

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“…Thus, the same growth cone may exhibit opposite turning responses to Netrin-1 depending on the levels of cytosolic cAMP. The adenosine receptor, A2b, has recently been shown to induce cAMP production after binding to Netrin-1 in vitro (Corset et al, 2000). Accordingly, it has been suggested that this interaction may represent one of the critical signaling events that regulates the attraction of growth cones to Netrin-1 (see Corset et al, 2000).…”

Section: Drosophila Ventral Nerve Cordmentioning

confidence: 99%

Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

146

108

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The central nervous system (CNS) of higher organisms is bilaterally-symmetric. The transfer of information between the two sides of the nervous system occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the CNS. Interestingly, these axons cross the midline only once. Other neurons extend axons that never cross the midline; they project exclusively on their own (ipsilateral) side of the CNS. Thus, the midline is an important choice point for several classes of pathfinding axons. Recent studies demonstrate that specialized midline cells play critical roles in regulating the guidance of both crossing and non-crossing axons at the ventral midline of the developing vertebrate spinal cord and the Drosophila ventral nerve cord. For example, these cells secrete attractive cues that guide commissural axons over long distances to the midline of the CNS. Furthermore, shortrange interactions between guidance cues present on the surfaces of midline cells, and their receptors expressed on the surfaces of pathfinding axons, allow commissural axons to cross the midline only once and prevent ipsilaterally-projecting axons from entering the midline. Remarkably, the molecular composition of commissural axon surfaces is dynamically-altered as they cross the midline. Consequently, commissural axons become responsive to repulsive midline guidance cues that they had previously ignored on the ipsilateral side of the midline. Concomitantly, commissural axons lose responsiveness to attractive guidance cues that had initially attracted them to the midline. Thus, these exquisitely regulated guidance systems prevent commissural axons from lingering within the confines of the midline and allow them to pioneer an appropriate pathway on the contralateral side of the CNS. Many aspects of midline guidance are controlled by mechanistically and evolutionarily-conserved ligand-receptor systems. Strikingly, recent studies demonstrate that these receptors are modular; the ectodomains determine ligand recognition and the cytoplasmic domains specify the response of an axon to a given guidance cue. Despite rapid and dramatic progress in elucidating the molecular mechanisms that control midline guidance, many questions remain.

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Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor

Cited by 197 publications

References 22 publications

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

The brain within the tumor: new roles for axon guidance molecules in cancers

Axon guidance at the midline choice point

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