title: NRC-interacting factor directs neurite outgrowth in an activity-dependent manner.
abstract: Nuclear hormone receptor coregulator-interacting factor 1 (NIF-1) is a zinc finger nuclear protein that was initially identified to enhance nuclear hormone receptor transcription via its interaction with nuclear hormone receptor coregulator (NRC). NIF-1 may regulate gene transcription either by modulating general transcriptional machinery or remodeling chromatin structure through interactions with specific protein partners. We previously reported that the cytoplasmic/nuclear localization of NIF-1 is regulated by the neuronal Cdk5 activator p35, suggesting potential neuronal functions for NIF-1. The present study reveals that NIF-1 plays critical roles in regulating neuronal morphogenesis at early stages. NIF-1 was prominently expressed in the nuclei of developing rat cortical neurons. Knockdown of NIF-1 expression attenuated both neurite outgrowth in cultured cortical neurons and retinoic acid (RA)-treated Neuro-2a neuroblastoma cells. Furthermore, activity-induced Ca(2+) influx, which is critical for neuronal morphogenesis, stimulated the nuclear localization of NIF-1 in cortical neurons. Suppression of NIF-1 expression reduced the up-regulation of neuronal activity-dependent gene transcription. These findings collectively suggest that NIF-1 directs neuronal morphogenesis during early developmental stages through modulating activity-dependent gene transcription.
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: X-S
authors.initials: XS
authors.lastname: Zhao
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Fu
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: K-W
authors.initials: KW
authors.lastname: Hung
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: W W Y
authors.initials: WW
authors.lastname: Chien
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: A K
authors.initials: AK
authors.lastname: Fu
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. Electronic address: BOIP@UST.HK.
authors.forename: N Y
authors.initials: NY
authors.lastname: Ip
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C000602985:Zfp335 protein, rat; C577646:Znf335 protein, mouse; D014212:Tretinoin; D002118:Calcium
keywords: gene transcription; neuronal development; neuronal morphogenesis; nuclear hormone receptor