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Signaling by neuronal swelling.

ABSTRACT: Several physical phenomena accompany the firing of electrical impulses by axons. Some of these, such as the microscopic swelling of axons, alter the transmission of light through axons. This produces what are called "intrinsic optical signals" because optical methods can be used to see axons fire without adding voltage-sensitive dyes or using electronic amplifiers. These physical changes allow neurons tocommunicate through nonsynaptic signals to adjacent cells, such as other neurons or glia. Two of the three videos in this Teaching Resource show the optical manifestations of the microscopic swelling of axons that accompanies the firing of action potentials in cultured neurons, and one shows the nonsynaptic release of ATP that occurs through membrane channels that are stimulated by neuronal swelling.

SUBMITTER: Fields RD

PROVIDER: S-EPMC3201844 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Signaling by neuronal swelling.

Fields R Douglas RD

Science signaling 20110111 155

Several physical phenomena accompany the firing of electrical impulses by axons. Some of these, such as the microscopic swelling of axons, alter the transmission of light through axons. This produces what are called "intrinsic optical signals" because optical methods can be used to see axons fire without adding voltage-sensitive dyes or using electronic amplifiers. These physical changes allow neurons tocommunicate through nonsynaptic signals to adjacent cells, such as other neurons or glia. Two ...[more]

PMID: 21224445

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Project description:The novel neuroproteasome is localized to the neuronal plasma membrane to degrade intracellular proteins into peptides that are released to the extracellular space. Selective inhibition of this neuronal membrane proteasome (NMP) complex ceased the release of peptides and rapidly attenuated neuronal transmission. Based on these findings, we hypothesize that these neuron-specific peptides mediate a novel form of communication through unique peptide-receptor interactions to promote intracellular signaling cascades relevant to neuronal development and function. Our work indicates that NMP peptides can rapidly induce N-methyl-D-aspartate receptor (NMDAR)-dependent calcium influx from dendrites to the soma, leading to rapid and sustained phosphorylation of the well-defined activity-dependent transcription factor cAMP response element-binding protein (CREB). We also determined that the gene expression program drastically changes upon NMP peptide treatment of neurons with an increase in expression of immediate early genes (e.g., Fos, Npas4, Egr4) known to have critical neuroregulatory roles. These data support our current thinking that NMP peptides are endogenous and selective activators of synaptic NMDA receptors and are critical for promoting activity-dependent gene expression. This pathway is orthogonal to the classic neurotransmitters previously described to activate NMDARs and points to NMP and its resulting peptides as key contributors to the development and function of the nervous system. However, the unique peptide sequences leading to neuronal activation are still poorly understood. Here, we show that the NMP peptides have tremendous sequence diversity through an unbiased peptidomic approach, and the current ongoing effort is to identify unique active peptide sequences with distinct receptor specificity. Elucidating the mechanism of the NMP and its active peptide products is crucial to understanding the role of this novel signaling process in the nervous system.

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Signaling by neuronal swelling.

Publications

Signaling by neuronal swelling.

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