Role of Megakaryoblastic Acute Leukemia-1 in ERK1/2-dependent Stimulation of Serum Response Factor-driven Transcription by BDNF or Increased Synaptic Activity

Overview

Journal J Neurosci

Specialty Neurology

Date 2006 Sep 29

PMID 17005865

Citations 48

Authors

Katarzyna Kalita

Giorgi Kharebava

Jing-Juan Zheng

Michal Hetman

Affiliations

Soon will be listed here.

Abstract

Serum response factor (SRF)-mediated transcription contributes to developmental and adult brain plasticity. Therefore, we investigated the role of a newly identified SRF coactivator, MKL1, in the regulation of SRF-driven transcription in rat forebrain neurons. MKL1 expression was found in newborn rat cortical or hippocampal neurons in culture as well as in adult rat forebrain. Immunostaining demonstrated constitutive nuclear localization of MKL1 in the CA1 region of the hippocampus, in the deep layers of the neocortex, and in cultured neurons. Overexpression of MKL1 in primary cortical neurons elevated SRF-driven transcription and enhanced its stimulation by BDNF. In addition, inhibition of endogenous MKL1 by overexpression of a dominant-negative MKL1 mutant or by small interfering RNA reduced BDNF activation of SRF-driven transcription. In neurons, endogenous MKL1 was associated with SRF-regulated chromatin regions of several endogenous genes including c-fos, JunB, Srf, and Cyr61. BDNF activation of MKL1/SRF-driven transcription was dependent on the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which also led to MKL1 phosphorylation. Finally, synaptic activity stimulation of SRF-driven transcription was reduced by inhibition of endogenous MKL1. Conversely, synaptic activity enhanced transcription by overexpressed MKL1. MKL1 regulation by synaptic activity was mediated through the NMDA receptor-activated ERK1/2. These results suggest that neuronal MKL1 contributes to SRF-regulated gene expression induced by BDNF or synaptic activity. In addition, MKL1 appears as a novel mediator of the signaling between ERK1/2 and SRF. Moreover, MKL1 is a likely regulator of SRF-driven transcription programs that underlie neuronal plasticity.

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References

Hanlon M, Sealy L . Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta. J Biol Chem. 1999; 274(20):14224-8. DOI: 10.1074/jbc.274.20.14224. View

Impey S, Obrietan K, Storm D . Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity. Neuron. 1999; 23(1):11-4. DOI: 10.1016/s0896-6273(00)80747-3. View

Hetman M, Kanning K, Cavanaugh J, Xia Z . Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J Biol Chem. 1999; 274(32):22569-80. DOI: 10.1074/jbc.274.32.22569. View

Morris T, Jafari N, Rice A, Vasconcelos O, DeLorenzo R . Persistent increased DNA-binding and expression of serum response factor occur with epilepsy-associated long-term plasticity changes. J Neurosci. 1999; 19(19):8234-43. PMC: 6783053. View

Graef I, Mermelstein P, Stankunas K, Neilson J, Deisseroth K, Tsien R . L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature. 1999; 401(6754):703-8. DOI: 10.1038/44378. View

Wang Y, Prywes R . Activation of the c-fos enhancer by the erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene. 2000; 19(11):1379-85. DOI: 10.1038/sj.onc.1203443. View

Kaplan D, Miller F . Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000; 10(3):381-91. DOI: 10.1016/s0959-4388(00)00092-1. View

Poser S, Impey S, Trinh K, Xia Z, Storm D . SRF-dependent gene expression is required for PI3-kinase-regulated cell proliferation. EMBO J. 2000; 19(18):4955-66. PMC: 314219. DOI: 10.1093/emboj/19.18.4955. View

Cavanaugh J, Ham J, Hetman M, Poser S, Yan C, Xia Z . Differential regulation of mitogen-activated protein kinases ERK1/2 and ERK5 by neurotrophins, neuronal activity, and cAMP in neurons. J Neurosci. 2001; 21(2):434-43. PMC: 6763829. View

10.

Adams J, Sweatt J . Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol. 2002; 42:135-63. DOI: 10.1146/annurev.pharmtox.42.082701.145401. View

11.

Valjent E, Caboche J, Vanhoutte P . Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular substrate for learning and memory?. Mol Neurobiol. 2002; 23(2-3):83-99. DOI: 10.1385/MN:23:2-3:083. View

12.

Brummelkamp T, Bernards R, Agami R . A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002; 296(5567):550-3. DOI: 10.1126/science.1068999. View

13.

Hardingham G, Fukunaga Y, Bading H . Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 2002; 5(5):405-14. DOI: 10.1038/nn835. View

14.

Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T . Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death. J Biol Chem. 2002; 277(32):28853-60. DOI: 10.1074/jbc.M203190200. View

15.

Lonze B, Ginty D . Function and regulation of CREB family transcription factors in the nervous system. Neuron. 2002; 35(4):605-23. DOI: 10.1016/s0896-6273(02)00828-0. View

16.

Markus A, Patel T, Snider W . Neurotrophic factors and axonal growth. Curr Opin Neurobiol. 2002; 12(5):523-31. DOI: 10.1016/s0959-4388(02)00372-0. View

17.

Hetman M, Hsuan S, Habas A, Higgins M, Xia Z . ERK1/2 antagonizes glycogen synthase kinase-3beta-induced apoptosis in cortical neurons. J Biol Chem. 2002; 277(51):49577-84. DOI: 10.1074/jbc.M111227200. View

18.

Miralles F, Posern G, Zaromytidou A, Treisman R . Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell. 2003; 113(3):329-42. DOI: 10.1016/s0092-8674(03)00278-2. View

19.

Shaw P, Saxton J . Ternary complex factors: prime nuclear targets for mitogen-activated protein kinases. Int J Biochem Cell Biol. 2003; 35(8):1210-26. DOI: 10.1016/s1357-2725(03)00031-1. View

20.

Miano J . Serum response factor: toggling between disparate programs of gene expression. J Mol Cell Cardiol. 2003; 35(6):577-93. DOI: 10.1016/s0022-2828(03)00110-x. View