Excitation-transcription coupling in smooth muscle.
ABSTRACT Calcium (Ca2+) signals affect virtually every biological process, including both contraction and gene transcription in smooth muscle. Ca2+-regulated gene transcription is known to be important for both physiological and pathological responses in smooth muscle. The aim of this review is to discuss the current understanding of gene transcription regulated by excitation through Ca2+ signalling using a comparison of the two most characterized Ca2+-regulated transcription factors in smooth muscle, Ca2+-cyclic AMP response element binding protein (CREB) and nuclear factor of activated T-cells (NFAT). Recent studies have shown commonalities and differences in the regulation of CREB and NFAT through both voltage- and non-voltage-gated Ca2+ channels that lead to expression of smooth muscle cell specific differentiation markers as well as markers of proliferation. New insights into the regulation of specific genes through companion elements on the promoters of Ca2+-regulated genes have led to new models for transcriptional regulation by Ca2+ that are defined both by the source and duration of the Ca2+ signal and the composition of enhancer elements found within the regulatory regions of specific genes. Thus the combination of signalling pathways elicited by particular Ca2+ signals affect selective promoter elements that are key to the ultimate pattern of gene transcription.
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ABSTRACT: Neurons generate particular calcium microdomains in response to different stimuli. Calcium microdomains have a central role in a variety of neuronal functions. In particular, calcium microdomains participate in long-lasting synaptic plasticity--a neuronal response presumably correlated with cognitive brain functions that requires expression of new gene products. Stimulation of skeletal muscle generates - with few milliseconds delay - calcium microdomains that have a central role in the ensuing muscle contraction. In addition, recent evidence indicates that sustained stimulation of skeletal muscle cells in culture generates calcium microdomains, which stimulate gene expression but not muscle contraction. The mechanisms whereby calcium microdomains activate signaling cascades that lead to the transcription of genes known to participate in specific cellular responses are the central topic of this review. Thus, we will discuss here the signaling pathways and molecular mechanisms, which via activation of particular calcium-dependent transcription factors regulate the expression of specific genes or set of genes in neurons or skeletal muscle cells.Cell Calcium 40(5-6):575-83. · 3.77 Impact Factor