Prestin is the motor protein of cochlear outer hair cells (OHCs) with the unique capability of performing direct, rapid and reciprocal electromechanical conversion. Prestin consists of 744 amino acids with a molecular mass of ~81.4 kDa. The predicted membrane topology and molecular mass of a single prestin molecule appear inadequate to account for the size of intramembrane particles (IMPs) expressed in the OHC membrane. Although recent biochemical evidence suggests that prestin forms homo-oligomers, most likely as a tetramer, the oligomeric structure of prestin in OHCs remains unclear. We obtained the charge density of prestin in the gerbil OHCs by measuring their nonlinear capacitance (NLC). The average charge density (22,608 μm−2) measured was four times the average IMP density (5,686 μm−2) reported in the freeze-fracture study. This suggests that each IMP contains four prestin molecules, based on the general notion that each prestin transfers a single elementary charge. We subsequently compared the voltage dependency and the values of slope factor of NLC and somatic motility simultaneously measured from the same OHCs to determine whether NLC and motility are fully coupled and how prestin subunits function within the tetramer. We showed that the voltage dependency and slope factors of NLC and motility were not statistically different, suggesting that NLC and motility are fully coupled. The fact that the slope factor is the same between NLC and motility suggests that each prestin monomer in the tetramer is in parallel, each interacting independently with cytoplasmic or other partners to facilitate the mechanical response.

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral non-sensory region. Here we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear non-sensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane, a flattened spiral prominence, and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the non-sensory epithelium covering the outer border Claudius cells, outer sulcus root cells and spiral prominence epithelial cells. Transcriptome analysis shows ZBTB20 regulates genes coding for tectorial membrane proteins in the greater epithelial ridge, and those preferentially expressed in root cells and spiral prominence epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral non-sensory domain.

Background The aim of this study was to assess the prognostic value of Krüppel-like factor 7 (KLF7) for patients with oral squamous cell carcinoma(OSCC). Methods The expression of KLF7 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of OSCC. Chi-square (χ2) test was applied to evaluate the association of KLF7 expression with clinicopathological characteristics of OSCC patients. Overall survival was estimated using the Kaplan-Meier method with log rank test. The cox proportional hazards model was used for univariate and multivariate analyses. Results The expression of KLF7 was remarkably increased in OSCC tissues compared with adjacent non-tumor tissues (P < 0.001). KLF7 expression was related to TNM stage (P = 0.006), tumor size (P = 0.010), smoking (P = 0.006) and drinking (P = 0.000). Kaplan-Meier analysis showed that OSCC patients with high KLF7 expression had a poorer overall survival than those with low expression (log rank test, P = 0.018). Moreover, multivariate analyses showed that KLF7 was an independent prognostic factor for OSCC (P = 0.002 HR = 2.645 95%CI: 1.426–4.906). Conclusion Decreased expression of KLF7 may be a potential unfavorable prognostic factor for patients with OSCC.