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Summary Transcriptional coactivator with PDZ‐binding motif (TAZ) directly interacts with transcription factors and regulates their transcriptional activity. Extensive functional studies have shown that TAZ plays critical regulatory roles in stem cell proliferation, differentiation, and survival and also modulates the development of organs such as the lung, kidney, heart, and bone. Despite the importance of TAZ in stem cell maintenance, TAZ function has not yet been evaluated in spermatogenic stem cells of the male reproductive system. Here, we investigated the expression and functions of TAZ in mouse testis. TAZ was expressed in spermatogenic stem cells; however, its deficiency caused significant structural abnormalities, including atrophied tubules, widened interstitial space, and abnormal Leydig cell expansion, thereby resulting in lowered sperm counts and impaired fertility. Furthermore, TAZ deficiency increased the level of apoptosis and senescence in spermatogenic cells and Leydig cells upon aging. The expression of senescence‐associated β‐galactosidase (SA‐βgal), secretory phenotypes, and cyclin‐dependent kinase inhibitors (p16, p19, and p21) significantly increased in the absence of TAZ. TAZ downregulation in testicular cells further increased SA‐βgal and p21 expression induced by oxidative stress, whereas TAZ overexpression decreased p21 induction and prevented senescence. Mechanistic studies showed that TAZ suppressed DNA‐binding activity of p53 through a direct interaction and thus attenuated p53‐induced p21 gene transcription. Our results suggested that TAZ may suppress apoptosis and premature senescence in spermatogenic cells by inhibiting the p53‐p21 signaling pathway, thus playing important roles in the maintenance and control of reproductive function.

Mitochondrial dynamics and mitophagy are thought to be important events for the quality control of mitochondria and mitochondria-associated diseases. To identify novel mitophagy modulators, we developed a cell-based screening system and selected 1,10-phenanthroline (Phen) as a target molecule. Phen treatment highly induced mitochondrial fragmentation and mitochondrial dysfunctions in a Drp1 dependent manner. Phen treatment also increased autophagy. Moreover, prolonged exposure of Phen increased mitochondria clearance through mitophagy. Phen-mediated loss of mitochondrial mass was more reduced in ATG5 deficient cells than in wild type cells. In addition, down-regulation of Drp1 decreased autophagy activation, suggesting that mitochondrial fission is involved in Phen-mediated mitophagy. Thus, our results demonstrate that the disruption of mitochondrial dynamics and mitochondrial dysfunctions provokes mitophagy in Phen-treated cells.

Airway epithelial cells regulate fluid and ion absorption and secretion to maintain pH and volume of airway surface liquid (ASL) (Smith & Welsh 1992, Van Scott et al. 1995, Coakley et al. 2003, Hunt 2006). The nasal epithelium, as part of the airway system, is known to actively secrete mucin and determine the electrolyte composition of nasal secretions. Disruption of these processes can lead to altered composition of nasal secretions and impairment of mucociliary clearance, common features of various nasal and paranasal diseases (Tos & Mogensen 1984). However, little is known about the mechanisms of fluid and electrolyte secretion and absorption in the human nasal epithelium. The anions HCO3− and Cl− are major constituents of cellular secretion and also affect ASL pH (Coakley & Boucher 2001). Various anion transporters, such as the anion exchangers (AEs), cystic fibrosis transmembrane conductance regulator (CFTR), sodium bicarbonate cotransporter (NBC) and calcium activated chloride channel (CaCC) are expressed in the human airway (Jacquot et al. 1993, Inglis et al. 2002, Mall et al. 2003, Paradiso et al. 2003). AEs translocate monovalent anions such as Cl− and HCO3− across the plasma membranes. Recent studies have identified two unrelated multigene families of AEs: the SLC4 and SLC26 transporters (Mount & Romero 2004, Alper 2006). The SLC4 transporter family of 10 genes includes three types of HCO3− transporters: AE (exchanges Cl− and HCO3−), NBC (transports Na+ and HCO3−) and Na+-driven Cl−–HCO3− exchangers (NDCBE). Four genes of this SLC4 family, SLC4A1, -A2, -A3 and SLC4A9, were reported as Cl−–HCO3− exchangers and these isoforms were named AE1, AE2, AE3 (bAE3 and cAE3) and AE4, respectively (Romero 2005). The SLC26 family consists of 10 genes (SLC26A1 to -A9 and -A11) encoding AEs that transport various anions including SO42−, Cl−, I−, OH− and HCO3− with variable specificity (Mount & Romero 2004). Among various isoforms, only AE2, bAE3 and SLC26A9 have been shown by RT-PCR to be expressed in human tracheobronchial tree and lung cancer cell lines (Al-Bazzaz et al. 2001, Lohi et al. 2002). Moreover, the possible effect of mucociliary differentiation on the expression of AE has not been reported in cultured airway epithelia. Recently, functional characterization of AEs has been investigated with pharmacological methods in various human cells and tissue including distal colon (Taylor et al. 2001) and pancreatic duct cell lines (Cheng et al. 1998). However, there are only a few reports on the function of AEs in the human airway, including the nasal epithelia (Loffing et al. 2000, Inglis et al. 2002, Mall et al. 2003). Therefore, the aim of this study was to investigate the regulation of mRNA expression of AEs in accordance with mucociliary differentiation, and the functional expression of AEs in both luminal and basolateral membranes in cultured normal human nasal epithelial (NHNE) cells. To this purpose, we first induced mucociliary differentiation of cultured NHNE cells and then confirmed differentiation with histological and molecular characterization. Next, we identified different types of AE isoforms present and any changes with respect to mucociliary differentiation in cultured NHNE cells. Finally, we examined the functional activity of AEs in the luminal and basolateral membranes of polarized monolayers of cultured NHNE cells.

A 70-year-old Japanese female developed tiny papules on her bilateral ears 2 years previously. A histological study of a biopsy specimen revealed that amorphous materials were present in the widened dermal papillae. Because these materials were positive for both Congo red and Dylon, we diagnosed the lesion as primary cutaneous amyloidosis of the auricular concha. Immunohistochemically, the amyloid substance stained positively with 34betaE12 (cytokeratin 1/5/10/14), suggesting that it had an epidermal origin. Seven reported cases of this unique disorder were also reviewed.