Reactome | Transcriptional Regulation by NPAS4

Transcriptional Regulation by NPAS4

Stable Identifier

R-HSA-9634815

DOI

10.3180/R-HSA-9634815.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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NPAS4 (Neuronal PAS domain containing protein 4) is a calcium dependent transcription factor predominantly expressed in neurons that regulates activation of genes involved in neuronal circuit formation, function, and plasticity (Ooe et al. 2004; Lin et al. 2008; Ramamoorthi et al. 2011; Maya-Vetencourt 2013; Sun and Lin 2016; Weng et al. 2018). NPAS4 possesses a conserved basic helix loop helix (bHLH) motif and a PAS domain (Fahim et al. 2018). NPAS4 is among the most rapidly induced immediate early genes (IEGs), which are activated after sensory and behavioral experience and thought to be crucial for formation of long term memory (Ramamoorthi et al. 2011; Sun et al. 2016; Heslin and Coutellier 2018; Weng et al. 2018). NPAS4 is activated within minutes of neuronal stimulation to regulate the formation of inhibitory synapses (Lin et al. 2008). NPAS4 enables gene regulation to be tailored to the type of depolarizing activity along the somato dendritic axis of a neuron (Brigidi et al. 2019). Transcriptional targets of NPAS4 include transcription factors and proteins involved in signal transduction and protein trafficking (Lin et al. 2008, Brigidi et al. 2019). NPAS4 regulates development of glutamatergic and GABAergic synapses essential for information processing and memory formation (Lin et al. 2008, Weng et al. 2018). NPAS4 induced gene expression programs differ between excitatory and inhibitory neurons (Spiegel et al. 2014), leading to a circuit wide homeostatic response. Besides directly regulating function of neurons, NPAS4 may be involved in the regulation of neuroinflammation and neuronal apoptosis (Zhang et al. 2009; Choy et al. 2015; Fan et al. 2016; Zhang et al. 2021). NPAS4 is expressed in the pancreatic beta cells and regulates their function under stress conditions (Sabatini et al. 2018). For review, please refer to Sun and Lin 2016, and Fu et al. 2020.

Literature References

PubMed ID	Title	Journal	Year
29298418	Neuronal PAS Domain Protein 4 Suppression of Oxygen Sensing Optimizes Metabolism during Excitation of Neuroendocrine Cells Wong, CK, Verchere, CB, Nian, C, Shapiro, AMJ, Sabatini, PV, Kin, T, Gibson, WT, Yoon, JS, Glavas, MM, Lynn, FC, Speckmann, T	Cell Rep	2018
26987258	Npas4: Linking Neuronal Activity to Memory Sun, X, Lin, Y	Trends Neurosci	2016
26690124	The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia Choy, FC, Klarić, TS, Koblar, SA, Lewis, MD	Int J Mol Sci	2015
19680447	Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity Lau, D, Zou, M, Descombes, P, Aso, Y, Lu, L, Ditzel, DA, Bading, H, Delucinge-Vivier, C, Zhang, SJ	PLoS Genet	2009
34418347	NPAS4 suppresses propofol-induced neurotoxicity by inhibiting autophagy in hippocampal neuronal cells Nie, L, Sun, J, Ji, D, Sun, N, Zhang, T, Song, J	Arch Biochem Biophys	2021
14701734	Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression Nakatuka, I, Ooe, N, Mikami, N, Kaneko, H, Saito, K	Mol. Cell. Biol.	2004
24855953	Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs Greenberg, ME, Spiegel, I, Gabel, HW, Harmin, DA, Tzeng, CP, Couch, CH, Mardinly, AR, Bazinet, JE	Cell	2014
29429933	Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation Dushko, M, Xu, W, Zemoura, K, Alviña, K, Chung, K, Lin, Y, Castillo, PE, Sørensen, AT, Lutzu, S, Yelhekar, TD, Zhang, Y, Rich, D, Garcia-Dominguez, D, Garcia, RI, Hung, M, Ku, T, Weng, FJ	Neuron	2018
26635026	NPAS4 Facilitates the Autophagic Clearance of Endogenous Tau in Rat Cortical Neurons Wang, X, Chen, G, Fan, W, Long, Y, Lai, Y, Zhu, B	J Mol Neurosci	2016
29227584	Npas4 deficiency and prenatal stress interact to affect social recognition in mice Heslin, K, Coutellier, L	Genes Brain Behav	2018
24024041	Activity-dependent NPAS4 expression and the regulation of gene programs underlying plasticity in the central nervous system Maya-Vetencourt, JF	Neural Plast	2013
18815592	Activity-dependent regulation of inhibitory synapse development by Npas4 Hauser, JL, Greenberg, ME, Kim, TK, Malik, AN, Hu, LS, Lin, Y, Bloodgood, BL, Koon, AC, Lapan, AD	Nature	2008
33335473	Essential Functions of the Transcription Factor Npas4 in Neural Circuit Development, Plasticity, and Diseases Zhen, J, Zhen, Z, Fu, J, Guo, O	Front Neurosci	2020
22194569	Npas4 regulates a transcriptional program in CA3 required for contextual memory formation Otto, T, McKinney, RM, Ramamoorthi, K, Fitzmaurice, HL, Lin, Y, Neve, RL, Belfort, GM, Fropf, R	Science	2011
29915698	Structural insights and characterization of human Npas4 protein Rashid, A, Rehman, Z, Ali, A, Virk, N, Fahim, A, Bhatti, MF, Paracha, RZ	PeerJ	2018
31585079	Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers Lin, PA, Brigidi, GS, Hayes, MGB, Bartlett, A, Bloodgood, BL, Heinz, S, Texari, L, Ecker, JR, Delos Santos, NP, Benner, C, Hartzell, AL	Cell	2019