Alternative titles; symbols
HGNC Approved Gene Symbol: ULK4
Cytogenetic location: 3p22.1 Genomic coordinates (GRCh38): 3:41,246,599-41,962,103 (from NCBI)
ULK4 belongs to a family of serine/threonine kinases (Lang et al., 2014).
Lang et al. (2014) identified several splice variants of ULK4 that encode serine/threonine kinases that differ at their C-terminal ends. The deduced 1,275-amino acid isoform is the longest. Immunohistochemical analysis detected ubiquitous expression of Ulk4 in mouse brain, with high intensity in layers II/III and V of cerebral cortex, in piriform cortex, CA1-3 of hippocampus, dentate gyrus, thalamic reticular nucleus, and ependymal cells lining the ventricles and choroid plexus. A similar expression pattern was detected in postmortem human brain, with ULK4 expression mainly located in postmitotic neurons. Western blot analysis of embryonic and adult mouse brains suggested a postnatal switch in Ulk4 isoform expression, with the smaller isoforms of approximately 105 kD and 95 kD expressed in the embryo and a larger isoform of approximately 130 kD expressed in the adult.
By Western blot analysis of SH-SY5Y human neuroblastoma cells, Lang et al. (2014) found that expression of the approximately 95-kD ULK4 isoform was elevated by 9-cis retinoic acid and all-trans retinoic acid. Knockdown of ULK4 in SH-SY5Y cells altered the composition of microtubules and reduced the length and branching of neurite extensions. ULK4 knockdown reduced cell motility and altered phosphorylation of ERK1 (601795)/ERK2 (176948), JNK (see 601158), and ELK1 (311040), and significantly upregulated phosphorylation of PKC (see 176960).
Lang et al. (2014) determined that the ULK4 gene has at least 36 exons.
Lang et al. (2014) stated that the ULK4 gene maps to chromosome 3p22.1.
Vogel et al. (2012) reported that the mouse Ulk4 gene maps to chromosome 9.
Vogel et al. (2012) found that Ulk4 knockout mice were smaller than normal sex-matched littermates, and all exhibited domed heads typical of hydrocephalus. The majority of Ulk4 knockout mice died before 4 months of age. Histologically, they showed severe dilatation and frequent hemorrhage of lateral and third ventricles. Hemorrhage was sometimes accompanied by fibrosis and neovascularization of meninges and choroid. Nasal passages and maxillary sinuses of Ulk4 knockout mice were partially filled with varying combinations of proteinaceous fluid or suppurative exudates. Suppurative otitis media was also present in many affected animals. Cilia were present on respiratory epithelium and ependymal cells lining the dilated ventricles, but they appeared to be shorter than those of wildtype littermates.
Lang et al. (2014) found that Ulk4 -/- mice had partial agenesis of the corpus callosum, with many areas lacking nerve fibers.
Lang, B., Pu, J., Hunter, I., Liu, M., Martin-Granados, C., Reilly, T. J., Gao, G.-D., Guan, Z.-L., Li, W.-D., Shi, Y.-Y., He, G., He, L., Stefansson, H., St Clair, D., Blackwood, D. H., McCaig, C. D., Shen, S. Recurrent deletions of ULK4 in schizophrenia: a gene crucial for neuritogenesis and neuronal motility. J. Cell Sci. 127: 630-640, 2014. [PubMed: 24284070] [Full Text: https://doi.org/10.1242/jcs.137604]
Vogel, P., Read, R. W., Hansen, G. M., Payne, B. J., Small, D., Sands, A. T., Zambrowicz, B. P. Congenital hydrocephalus in genetically engineered mice. Vet. Path. 49: 166-181, 2012. [PubMed: 21746835] [Full Text: https://doi.org/10.1177/0300985811415708]