Lipid Rafts Mediate Chemotropic Guidance of Nerve Growth Cones

Guirland, Carmine; Suzuki, Shingo; Kojima, Masami; Lu, Bai; Zheng, James

doi:10.1016/s0896-6273(04)00248-x

Cited by 46 publications

(73 citation statements)

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“…Of particular interest is the comparison between the neurotrophin BDNF and netrin because both cues produce a more complex axon arbor with increased synapse density and they share many common signaling mechanisms (Caroni, 1998; Meyer-Franke et al, 1998; Ming et al, 1999; Ming et al, 2002; Nishiyama et al, 2003; Guirland et al, 2004; Jin et al, 2005; Shim et al, 2005; Wang and Poo, 2005), but the changes in axon dynamics they produce are significantly different. BDNF exerts rapid and significant effects on the addition and stability of presynaptic sites and axon branches (within 2 hours of treatment).…”

Section: Discussionmentioning

confidence: 99%

Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain

Manitt

Nikolakopoulou²,

Almario³

et al. 2009

J. Neurosci.

104

110

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Netrin has been implicated in retinal ganglion cell (RGC) axon pathfinding in a number of species. In Xenopus laevis, RGC axons reaching their target in the optic tectum can be repelled by a netrin-1 gradient in vitro, suggesting that netrin may also function in wiring events that follow successful axon pathfinding. Here, we examined the contribution of netrin to RGC axon arborization and synapse formation at the target. Time-lapse confocal microscopy imaging of individual RGC axons coexpressing GFP-synaptobrevin and DsRed in the intact Xenopus brain demonstrated a role for deleted in colorectal cancer (DCC)-mediated netrin signaling. Microinjection of netrin-1 into the tectum induced a rapid and transient increase in presynaptic site addition that resulted in higher presynaptic site density over a 24 h observation period. Moreover, netrin induced dynamic axon branching, increasing branch addition and retraction; a behavior that ultimately increased total branch number. In contrast, microinjection of DCC function-blocking antibodies prevented the increase in presynaptic site number normally observed in control axons as well as the associated increase in branch number and axon arbor growth. Dynamic analysis of axon arbors demonstrated that the effects of anti-DCC on axon morphology and presynaptic connectivity were attributable to a specific decrease in new synapse and branch additions, without affecting the stability of existing synapses and branches. Together, these results indicate that, in the absence of DCC signaling, RGC axons fail to branch and differentiate, and support a novel role for netrin in later phases of retinotectal development.

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Section: Discussionmentioning

confidence: 99%

Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain

Manitt

Nikolakopoulou²,

Almario³

et al. 2009

J. Neurosci.

104

110

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“…MAG-binding gangliosides are localized on the axolemmal surface of myelinated axons and Schwann cells (Sheikh, Deerinck et al 1999). Interestingly, perturbation of lipid rafts and gangliosides in neuronal growth cones disrupts their responses to guidance cues (Guirland, Suzuki et al 2004), suggesting a role of MAG/gangliosides signaling at neuronal growth cones, and possibly at regenerating growth cones as well. Consistent with this notion, interference of MAG function with a MAG-antibody enhances target reinnervation of regenerating axons and enhanced functional recovery (Mears, Schachner et al 2003).…”

Section: Role Of Cell Surface Receptors In Growth Cones During Pns Axmentioning

confidence: 99%

Roles of channels and receptors in the growth cone during PNS axonal regeneration

Shim

Ming

2010

Experimental Neurology

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Neurons in the peripheral nervous system (PNS) are known to maintain a regenerative capacity and will normally regenerate their axons within a permissive growth environment. The success of regeneration in the PNS largely depends on maintenance of the supportive basal lamina membrane, efficient removal of axonal and myelin debris by macrophages and Schwann cells, expression of neurotrophic factors by Schwann cells, and up-regulation of the intrinsic growth program in PNS neurons. The PNS regenerative process is well characterized through initial Wallerian degeneration followed by axonal sprouting, formation of neuronal growth cones, active axonal growth to the target, and finally sensory and motor functional recovery. The initiation and maintenance of active growth cones during peripheral nerve regeneration recapitulates many aspects of early neural development and is achieved through the activation of complex signaling cascades, involving various receptors, channels, cytoplasmic signaling cascades, as well as transcriptional and translational programs. This review focuses on roles of cell surface ion channels and receptors in the growth cone during Wallerian degeneration and axon regeneration in the PNS.

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“…The asymmetric localization of actin-mRNAs have been reported, suggesting that GC steering follows a local and polarized translation [20], [21]. Similarly, in the presence of a BDNF (Brain-Derived Neurotrophic Factor) gradient, membrane receptors preferentially associated to lipid rafts localized on the side of the GC facing the gradient source [22], possibly causing a modulation of the cell response [23]. However, the mechanisms by which molecules (proteins, mRNAs,…) or organelles are asymmetrically translocated remain unclear.…”

Section: Introductionmentioning

confidence: 98%

A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

2010

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Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals.

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Lipid Rafts Mediate Chemotropic Guidance of Nerve Growth Cones

Cited by 46 publications

References 0 publications

Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain

Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain

Roles of channels and receptors in the growth cone during PNS axonal regeneration

A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

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