BIO254:Transcription

Introduction

In activity-dependent transcription, a postsynaptic neuron changes its transcription of specific genes in response to synaptic activity. Both long-term and short-term changes are produced by synaptic activity. Long-term changes, such as synaptic plasticity and neuronal development, are often caused by changes in gene expression.

General Mechanism for Activity-Dependent Transcription

Following are the steps between the neuronal activity and the changes in gene expression:

A) Neuronal Activity

The presynaptic neuron excites or inhibits the postsynaptic neuron using neurotransmitters, such as glutamate or GABA.

B) Postsynaptic Response

The neurotransmitter activates metabotropic and/or ionotropic receptors activating G-protein/second messenger systems or producing ionic currents, respectively.

C) Signaling Pathways

Signaling proteins are activated (phosporylated/dephosphorylated) by either the G-protein pathways or the pathways affected by ionic concentrations (usually Ca2+ dependent). These pathways are often referred to as cascades because of the multiple proteins phosphorylated/dephosphorylated sequentially in a pathway.

D) Nuclear Localization

An activated protein enters the nucleus and activates/inactivates an activating or repressing transcription factor. In some cases, the protein that enters the nucleus is itself an activated transcription factor which goes directly and binds to its specific DNA sequence.

E) Transcription Factor Binding/Unbinding to DNA

The transcription factor then binds to or breaks away from the DNA, depending on whether the transcription factor was activated or inactivated, respectively.

F) Gene expression Increased/Decreased

Depending on whether the transcription factor is activated or inactivated and whether the transcription factor itself activates or represses gene expression, the transcription of the target gene(s) will be changed.

Examples of Pathways that Affect Transcription

Activation of CREB

Images of CREB Pathway: Biocarta Panomics Sigma Aldrich UT Houston Humboldt University, Berlin Eurekah

Abbreviations used: CREB: cAMP responsive element binding protein CBP: CREB binding protein ROS: reactive oxygen species PKA: protein kinase A ERK: extracellular regulated kinase MEK: MAPK kinase PI3-K: phopshatidyl inositol3 kinase GSK3: glycogen synthase kinase 3B CaM: calmodulin Ca2+/CaM: calcium calmodulin (calcium bound to calmodulin) CaMKK: calmodulin kinase kinase CaMKIV:

History

Notes

This article has focused on activity-dependent transcription in neurons. Activity-dependent transcription occurs in various excitable cells, such as muscle cells (ie, Wamhoff et. al. 2006).

References

Wamhoff BR, Bowles DK, Owens GK. Excitation-transcription coupling in arterial smooth muscle. Circ Res. 2006 Apr 14;98(7):868-78.

Squire LR, et al. Fundamental Neuroscience. Academic Press, Boston, 2003.

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