Neuronal PAS domain protein 4 explained

Neuronal PAS domain protein 4 is a protein that in humans is encoded by the NPAS4 gene.^[1] The NPAS4 gene is a neuronal activity-dependent immediate early gene that has been identified as a transcription factor. The protein regulates the transcription of genes that control inhibitory synapse development, synaptic plasticity and most recently reported also behavior.^[2]

Function

NPAS4 is a member of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008].

NPAS4 has been shown by Dr. Brenda Bloodgood to play critical roles in regulating the plasticity of inhibitory neurons. She found that NPAS4 helps to regulate plasticity by orchestrating a redistribution of inhibitory synapses, wherein they are lost from proximal apical dendrites of CA1 pyramidal neurons and increased on the somata.^[3]

Further reading

• Ooe N, Saito K, Mikami N, Nakatuka I, Kaneko H . 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 . Mol. Cell. Biol. . 24 . 2 . 608–16 . 2004 . 14701734 . 343817 . 10.1128/mcb.24.2.608-616.2004.
• Bersten DC, Bruning JB, Peet DJ, Whitelaw ML . Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function . PLOS ONE . 9 . 1 . e85768 . 2014 . 24465693 . 3894988 . 10.1371/journal.pone.0085768 . free . 2014PLoSO...985768B .
• Klaric TS, Thomas PQ, Dottori M, Leong WK, Koblar SA, Lewis MD . A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells . Stem Cell Res Ther . 5 . 3 . 64 . 2014 . 24887558 . 4076635 . 10.1186/scrt453 . free .
• Funahashi Y, Ariza A, Emi R, Xu Y, Shan W, Suzuki K, Kozawa K, Ahammad RU, Wu M, Takano T, Yura Y, Kuroda K, Nagai T, Amano M, Yamada K, Kaibuchi K . Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors . Cell Reports . 29 . 10 . 3235–3252.e9 . 2019 . 10.1016/j.celrep.2019.10.116 . 31801086 . free .

Notes and References

1. Web site: Entrez Gene: Neuronal PAS domain protein 4. 2017-10-15.
2. Funahashi Y, Ariza A, Emi R, Xu Y, Shan W, Suzuki K, Kozawa K, Ahammad RU, Wu M, Takano T, Yura Y, Kuroda K, Nagai T, Amano M, Yamada K, Kaibuchi K . Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors . Cell Reports . 29 . 10 . 3235–3252.e9 . 2019 . 31801086 . 10.1016/j.celrep.2019.10.116 . free .
3. Bloodgood. Brenda L.. Sharma. Nikhil. Browne. Heidi Adlman. Trepman. Alissa Z.. Greenberg. Michael E.. 2013-11-07. The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature. 503. 7474. 121–125. 10.1038/nature12743. 1476-4687. 4169177. 24201284. 2013Natur.503..121B .