Alternative titles; symbols
HGNC Approved Gene Symbol: KLHL17
Cytogenetic location: 1p36.33 Genomic coordinates (GRCh38): 1:960,584-965,719 (from NCBI)
KLHL17 is a neuron-specific protein that modulates F-actin remodeling and contributes to regulation of neuronal morphogenesis, maturation, and activity (Hu et al., 2020).
Dhanoa et al. (2013) reported that human KLHL17 contains 642 amino acids. It has an N-terminal BTB domain, followed by a BACK domain and 6 C-terminal Kelch motifs. The authors noted that BTB domains facilitate protein binding and dimerization and that Kelch domains form a beta-propeller structure involved in extracellular functions, morphology, and protein binding.
By immunoblot analysis of mouse tissues, Hu et al. (2020) showed that Klhl17, or actinfilin, was predominantly expressed in brain. Immunostaining revealed that endogenous and exogenous Klhl17 formed puncta in the soma and along dendrites of cultured mouse and rat neurons. Confocal microscopy showed that Klhl17 puncta were distributed at dendritic spines and along the dendritic shaft, with some colocalization with or adjacent to F-actin.
Dhanoa et al. (2013) stated that the KLHL17 gene maps to chromosome 1p36.33.
Hu et al. (2020) noted that the N-terminal BTB domain of KLHL17 is involved in dimerization and cullin-3 (CUL3; 603136) binding, and that the C-terminal Kelch repeats are involved in binding to F-actin and substrates of CUL3-dependent E3 ubiquitin ligase. By coimmunoprecipitation analysis, Hu et al. (2020) confirmed that the Kelch repeats of rat Klhl17 interacted with actin in transfected Neuro2A mouse neuroblastoma cells. Knockdown of Klhl17 in Neuro2A cells and cultured mouse and rat neurons impaired dendritic spine enlargement, but not density or length of dendritic spines. Moreover, Klhl17 knockdown reduced F-actin enrichment and pre- and postsynaptic markers at dendritic spines. Mutation analysis showed that both the BTB domain and Kelch repeats of Klhl17 were required for F-actin remodeling and enrichment at dendritic spines and for dendritic spine enlargement.
Hu et al. (2020) found that neurons from Klhl17 -/- and Klhl17 +/- mice had reduced width of dendritic spine heads and reduced pre- and postsynaptic markers compared with wildtype. Miniature excitatory postsynaptic current (mEPSC) frequency was comparable in Klhl17 +/- and wildtype neurons, but mEPSC amplitude was slightly increased in Klhl17 +/- neurons. Klhl17 +/- mice exhibited hyperactivity and reduced social interaction, supporting a role for Klhl17 in regulating mouse brain function and behavior.
Dhanoa, B. S., Cogliati, T., Satish, A. G., Bruford, E. A., Friedman, J. S. Update on the Kelch-like (KLHL) gene family. Hum. Genomics 7: 13, 2013. Note: Electronic Article. [PubMed: 23676014] [Full Text: https://doi.org/10.1186/1479-7364-7-13]
Hu, H.-T., Huang, T.-N., Hsueh, Y.-P. KLHL17/actinfilin, a brain-specific gene associated with infantile spasms and autism, regulates dendritic spine enlargement. J. Biomed. Sci. 27: 103, 2020. Note: Electronic Article. [PubMed: 33256713] [Full Text: https://doi.org/10.1186/s12929-020-00696-1]