Send to

Choose Destination
Front Cell Neurosci. 2019 Jul 31;13:348. doi: 10.3389/fncel.2019.00348. eCollection 2019.

Functional Dissection of C. elegans bZip-Protein CEBP-1 Reveals Novel Structural Motifs Required for Axon Regeneration and Nuclear Import.

Author information

Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, United States.
Department of Biology, Utrecht University, Utrecht, Netherlands.
Convergence Program of Material Science for Medicine and Pharmaceutics, Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, South Korea.


The basic leucine-zipper (bZIP) domain transcription factors CCAAT/enhancer-binding proteins (C/EBP) have a variety of roles in cell proliferation, differentiation, and stress response. In the nervous system, several isoforms of C/EBP function in learning and memory, neuronal plasticity, neuroinflammation, and axon regeneration. We previously reported that the Caenorhabditis elegans C/EBP homolog, CEBP-1, is essential for axon regeneration. CEBP-1 consists of 319 amino acids, with its bZIP domain at the C-terminus and a long N-terminal fragment with no known protein motifs. Here, using forward genetic screening with targeted genome editing, we have identified a unique domain in the N-terminus that is critical for its in vivo function. Additionally, we characterized three nuclear localization signals (NLS) in CEBP-1 that act together to mediate CEBP-1's nuclear import. Moreover, the Importin-α, IMA-3, can bind to CEBP-1 via one of the NLS. ima-3 is ubiquitously expressed in all somatic cells, and ima-3 null mutants are larval lethal. Using Cre-lox dependent neuron-specific deletion strategy, we show that ima-3 is not critical for axon development, but is required for axon regeneration in adults. Together, these data advance our understanding of CEBP-1's function, and suggest new regulators that remain to be identified to expand the CEBP-1 protein interactome.


C/EBP; IMA-3; NIPI-3; Tribbles; importin; nuclear localization; structural-function domain

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center