Alternative titles; symbols
HGNC Approved Gene Symbol: NEURL4
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,315,628-7,329,335 (from NCBI)
Centrosomes are composed of an older mother centriole and a younger daughter centriole surrounded by pericentriolar material. Centrosomes function as primary microtubule-organizing centers during mitosis by organizing the assembly of bipolar spindles essential for equal chromosome segregation. NEURL4 localizes to the daughter centriole and prevents formation of ectopic microtubule-organizing centers (Li et al., 2012).
By sequencing clones obtained from a size-fractionated human fetal brain cDNA library, Nagase et al. (2001) cloned NEURL4, which they designated KIAA1787. The deduced protein contains 1,564 amino acids. RT-PCR ELISA detected high NEURL4 expression in all adult and fetal tissues and all specific adult brain regions examined.
Using mass spectrometry, Li et al. (2012) identified NEURL4 as a protein that interacted with the centrosomal capping protein CP110 (609544). NEURL4 has 6 highly conserved neuralized homology repeats (NHRs), which are thought to mediate protein-protein interactions. Western blot analysis of human cell lines detected NEURL4 at an apparent molecular mass of approximately 170 kD. NEURL4 preferentially associated with markers of the daughter centriole in both growing and quiescent human cell lines and was excluded from basal bodies.
Using reciprocal immunoprecipitation analysis, Li et al. (2012) confirmed that NEURL4 and CP110 interacted directly. Mutation analysis revealed that NHR3 was predominantly responsible for interaction of NEURL4 with CP110. Knockdown of NEURL4 in human cell lines caused ectopic formation and amplification of microtubule-organizing centers and increased CP110 content, resulting in abnormal mitoses with pseudobipolar spindles and lagging chromosomes. Codepletion of CP110 and NEURL4 corrected the defects, suggesting that the phenotype was dependent on elevated cellular CP110 content. In contrast, overexpression of NEURL4 promoted ubiquitination and degradation of CP110 and reduced CP110 association with centrioles.
Hartz (2014) mapped the NEURL4 gene to chromosome 17p13.1 based on an alignment of the NEURL4 sequence (GenBank AL833570) with the genomic sequence (GRCh37).
Hartz, P. A. Personal Communication. Baltimore, Md. 6/26/2014.
Li, J., Kim, S., Kobayashi, T., Liang, F.-X., Korzeniewski, N., Duensing, S., Dynlacht, B. D. Neurl4, a novel daughter centriole protein, prevents formation of ectopic microtubule organizing centres. EMBO Rep. 13: 547-553, 2012. [PubMed: 22441691] [Full Text: https://doi.org/10.1038/embor.2012.40]
Nagase, T., Nakayama, M., Nakajima, D., Kikuno, R., Ohara, O. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 8: 85-95, 2001. [PubMed: 11347906] [Full Text: https://doi.org/10.1093/dnares/8.2.85]