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1.
Genotype–phenotype correlations for <Emphasis Type="Italic">SLC26A4-</Emphasis>related deafness 总被引:1,自引:0,他引:1
Azaiez H Yang T Prasad S Sorensen JL Nishimura CJ Kimberling WJ Smith RJ 《Human genetics》2007,122(5):451-457
Pendred syndrome (PS) and non-syndromic enlarged vestibular aqueduct (EVA) are two recessive disorders characterized by the
association of sensorineural hearing loss (SNHL) with inner ear malformations that range from isolated EVA to Mondini Dysplasia,
a complex malformation that includes a cochlear dysplasia and EVA. Mutations in the SLC26A4 gene, coding for the protein pendrin, have been implicated in the pathophysiology of both disorders. In order to determine
whether SLC26A4 genotypes can be correlated to the complexity and severity of the phenotypes, we ascertained 1,506 deaf patients. Inner ear
abnormalities were present in 474 patients (32%). Mutation screening of SLC26A4 detected two mutations in 16% of patients, one mutation in 19% of patients and zero mutation in 65% of patients. When the
distribution of SLC26A4 genotypes was compared across phenotypes, a statistically significant difference was found between PS patients and non-syndromic
EVA–Mondini patients (P = 0.005), as well as between EVA patients and Mondini patients (P = 0.0003). There was a correlation between phenotypic complexity of inner ear malformations and genetic heterogeneity—PS
patients have the most severe phenotype and the most homogeneous etiology while EVA patients have the least severe phenotype
and the most heterogeneous etiology. For all patients, variability in the degree of hearing loss is seen across genotypes
implicating other genetic and/or environmental factors in the pathogenesis of the PS–Mondini–EVA disease spectrum. 相似文献
2.
SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct 总被引:1,自引:0,他引:1
Ito T Choi BY King KA Zalewski CK Muskett J Chattaraj P Shawker T Reynolds JC Butman JA Brewer CC Wangemann P Alper SL Griffith AJ 《Cellular physiology and biochemistry》2011,28(3):545-552
Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene. SLC26A4 mutations may also be identified in some patients with nonsyndromic EVA (NSEVA). The presence of two mutant alleles of SLC26A4 is correlated with bilateral EVA and Pendred syndrome, whereas unilateral EVA and NSEVA are correlated with one (M1) or zero (M0) mutant alleles of SLC26A4. Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients. In M1 families, EVA may be associated with a second, undetected SLC26A4 mutation or epigenetic modifications. In M0 families, there is probably etiologic heterogeneity that includes causes other than, or in addition to, monogenic inheritance. 相似文献
3.
Xiangming Li Joel D. Sanneman Donald G. Harbidge Fei Zhou Taku Ito Raoul Nelson Nicolas Picard Régine Chambrey Dominique Eladari Tracy Miesner Andrew J. Griffith Daniel C. Marcus Philine Wangemann 《PLoS genetics》2013,9(7)
Mutations of SLC26A4 are a common cause of human hearing loss associated with enlargement of the vestibular aqueduct. SLC26A4 encodes pendrin, an anion exchanger expressed in a variety of epithelial cells in the cochlea, the vestibular labyrinth and the endolymphatic sac. Slc26a4
Δ/Δ mice are devoid of pendrin and develop a severe enlargement of the membranous labyrinth, fail to acquire hearing and balance, and thereby provide a model for the human phenotype. Here, we generated a transgenic mouse line that expresses human SLC26A4 controlled by the promoter of ATP6V1B1. Crossing this transgene into the Slc26a4
Δ/Δ line restored protein expression of pendrin in the endolymphatic sac without inducing detectable expression in the cochlea or the vestibular sensory organs. The transgene prevented abnormal enlargement of the membranous labyrinth, restored a normal endocochlear potential, normal pH gradients between endolymph and perilymph in the cochlea, normal otoconia formation in the vestibular labyrinth and normal sensory functions of hearing and balance. Our study demonstrates that restoration of pendrin to the endolymphatic sac is sufficient to restore normal inner ear function. This finding in conjunction with our previous report that pendrin expression is required for embryonic development but not for the maintenance of hearing opens the prospect that a spatially and temporally limited therapy will restore normal hearing in human patients carrying a variety of mutations of SLC26A4. 相似文献
4.
Pendred syndrome (PS) is an autosomal recessive disorder characterized by congenital bilateral sensorineural hearing loss, goiter, and incomplete iodide organification. Patients with PS also have structural anomalies of the inner ear such as enlarged vestibular aqueducts (EVA) and Mondini's malformation. The goiter, which is a major clinical manifestation of PS, usually develops around adolescence. PS is caused by biallelic mutations of the SLC26A4 gene, while nonsyndromic bilateral EVA is associated with zero or one SLC26A4 mutant allele. We report here a Korean family including a young female with PS who had goiter and progressive, fluctuating sensorineural hearing loss that could be partially recovered by oral steroid treatment. Genetic investigation revealed compound heterozygous mutations for p.R677AfsX11, a novel frameshift mutation, and p.H723R in the SLC26A4 gene. Our findings provide detailed information regarding the distribution of mutant alleles for PS and may serve as a foundation for studies to comprehend the genetic portion of syndromic hearing loss. 相似文献
5.
Tao Yang Jose G. Gurrola II Sui M. Chiu Peter M. Snyder 《American journal of human genetics》2009,84(5):651-657
Mutations in SLC26A4 cause nonsyndromic hearing loss associated with an enlarged vestibular aqueduct (EVA, also known as DFNB4) and Pendred syndrome (PS), the most common type of autosomal-recessive syndromic deafness. In many patients with an EVA/PS phenotype, mutation screening of SLC26A4 fails to identify two disease-causing allele variants. That a sizable fraction of patients carry only one SLC26A4 mutation suggests that EVA/PS is a complex disease involving other genetic factors. Here, we show that mutations in the inwardly rectifying K+ channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an EVA/PS phenotype. In probands from two families, we identified double heterozygosity in affected individuals. These persons carried single mutations in both SLC26A4 and KCNJ10. The identified SLC26A4 mutations have been previously implicated in EVA/PS, and the KCNJ10 mutations reduce K+ conductance activity, which is critical for generating and maintaining the endocochlear potential. In addition, we show that haploinsufficiency of Slc26a4 in the Slc26a4+/− mouse mutant results in reduced protein expression of Kcnj10 in the stria vascularis of the inner ear. Our results link KCNJ10 mutations with EVA/PS and provide further support for the model of EVA/PS as a multigenic complex disease. 相似文献
6.
Dossena S Nofziger C Tamma G Bernardinelli E Vanoni S Nowak C Grabmayer E K?ssler S Stephan S Patsch W Paulmichl M 《Cellular physiology and biochemistry》2011,28(3):451-466
Pendrin (SLC26A4, PDS) is an electroneutral anion exchanger transporting I(-), Cl(-), HCO(3)(-), OH(-), SCN(-) and formate. In the thyroid, pendrin is expressed at the apical membrane of the follicular epithelium and may be involved in mediating apical iodide efflux into the follicle; in the inner ear, it plays a crucial role in the conditioning of the pH and ion composition of the endolymph; in the kidney, it may exert a role in pH homeostasis and regulation of blood pressure. Mutations of the pendrin gene can lead to syndromic and non-syndromic hearing loss with EVA (enlarged vestibular aqueduct). Functional tests of mutated pendrin allelic variants found in patients with Pendred syndrome or non-syndromic EVA (ns-EVA) revealed that the pathological phenotype is due to the reduction or loss of function of the ion transport activity. The diagnosis of Pendred syndrome and ns-EVA can be difficult because of the presence of phenocopies of Pendred syndrome and benign polymorphisms occurring in the general population. As a consequence, defining whether or not an allelic variant is pathogenic is crucial. Recently, we found that the two parameters used so far to assess the pathogenic potential of a mutation, i.e. low incidence in the control population, and substitution of evolutionary conserved amino acids, are not always reliable for predicting the functionality of pendrin allelic variants; actually, we identified mutations occurring with the same frequency in the cohort of hearing impaired patients and in the control group of normal hearing individuals. Moreover, we identified functional polymorphisms affecting highly conserved amino acids. As a general rule however, we observed a complete loss of function for all truncations and amino acid substitutions involving a proline. In this view, clinical and radiological studies should be combined with genetic and molecular studies for a definitive diagnosis. In performing genetic studies, the possibility that the mutation could affect regions other than the pendrin coding region, such as its promoter region and/or the coding regions of functionally related genes (FOXI1, KCNJ10), should be taken into account. The presence of benign polymorphisms in the population suggests that genetic studies should be corroborated by functional studies; in this context, the existence of hypo-functional variants and possible differences between the I(-)/Cl(-) and Cl(-)/HCO(3)(-) exchange activities should be carefully evaluated. 相似文献
7.
Silvia Dossena Valeria Vezzoli Nadia Cerutti Claudia Bazzini Marisa Tosco Chiara Sironi Simona Rodighiero Giuliano Meyer Umberto Fascio Johannes Fürst Markus Ritter Laura Fugazzola Luca Persani Patrick Zorowka Carlo Storelli Paolo Beck-Peccoz Guido Bottà Markus Paulmichl 《Cellular physiology and biochemistry》2006,17(5-6):245-256
BACKGROUND: Malfunction of the SLC26A4 protein leads to prelingual deafness often associated with mild thyroid dysfunction and goiter. It is assumed that SLC26A4 acts as a chloride/anion exchanger responsible for the iodide organification in the thyroid gland, and conditioning of the endolymphatic fluid in the inner ear. METHODS: Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss. RESULTS: Experiments are summarized showing the functional characterization of wild type SLC26A4 and a mutant (S28R), which we described recently. This mutant protein is transposed towards the cell membrane, however, its transport capability is markedly reduced if compared to wild-type SLC26A4. Furthermore, we show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes with iodide, and, in addition, that the chloride uptake can be blocked by NPPB and niflumic acid, whereas DIDS is ineffective. CONCLUSIONS: The functional characteristics of SLC26A4(S28R) we describe here, are consistent with the clinical phenotype observed in the patient from which the mutant was derived. 相似文献
8.
Dossena S Nofziger C Lang F Valenti G Paulmichl M 《Cellular physiology and biochemistry》2011,28(3):377-384
Human pendrin (SCL26A4, PDS) is a 780 amino acid integral membrane protein with transport function. It acts as an electroneutral, sodium-independent anion exchanger for a wide range of anions, such as iodide, chloride, formate, bicarbonate, hydroxide and thiocyanate. Pendrin expression was originally described in the thyroid gland, kidney and inner ear. Accordingly, pendrin mutations with reduction or loss of transport function result in thyroid and inner ear abnormalities, manifested as syndromic (Pendred syndrome) and non-syndromic hearing loss with an enlarged vestibular aqueduct (ns-EVA). Pendred syndrome, the most common form of syndromic deafness, is an autosomal recessive disease characterized by sensorineural deafness due to inner ear malformations and a partial iodide organification defect that may lead to thyroid goiter. Later, it became evident that not only pendrin loss of function, but also up-regulation could participate in the pathogenesis of human diseases. Indeed, despite the absence of kidney dysfunction in Pendred syndrome patients, evidence exists that pendrin also plays a crucial role in this organ, with a potential involvement in the pathogenesis of hypertension. In addition, recent data underscore the role of pendrin in exacerbations of respiratory distresses including bronchial asthma and chronic obstructive pulmonary disease (COPD). Pendrin expression in other organs such as mammary gland, testis, placenta, endometrium and liver point to new, underscored pendrin functions that deserve to be further investigated. 相似文献
9.
10.
Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders
O. L. Mironovich E. A. Bliznetz T. G. Markova E. N. Geptner M. R. Lalayants E. I. Zelikovich G. A. Tavartkiladze A. V. Polyakov 《Russian Journal of Genetics》2017,53(1):128-138
Pendred syndrome is an autosomal recessive inherited disorder characterized by a combination of sensorineural hearing impairment and euthyroid goiter; its clinical manifestation in children is hardly distinguishable from nonsyndromic hearing loss. Pendred syndrome is one of the most frequent types of syndromic hearing loss. Hearing impairment is accompanied by abnormal development of the bony labyrinth—enlarged vestibular aqueduct (EVA) and occasionally combined with Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin protein, are responsible for both Pendred syndrome and for allelic disorder (nonsyndromic enlarged vestibular aqueduct). The present study for the first time conducted molecular genetic analysis in 20 Russian patients with Pendred syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in the SLC26A4 gene were revealed in four patients. The mutation c.222G>T (p.Trp74Cys) was detected for the first time. Mutations were found in patients with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia. Mutations were not detected in patients with isolated Mondini dysplasia. One proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG mutation in the GJB2 gene. The absence of frequent mutations, including well-known ones or “hot” exons in the SLC26A4 gene, was reported. Therefore, the optimal method to search for mutations in the SLC26A4 gene in Russian patients is Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene. 相似文献
11.
12.
Silvia Dossena Simona Rodighiero Valeria Vezzoli Claudia Bazzini Chiara Sironi Giuliano Meyer Johannes Fürst Markus Ritter Maria L Garavaglia Laura Fugazzola Luca Persani Patrick Zorowka Carlo Storelli Paolo Beck-Peccoz Guido Bottá Markus Paulmichl 《Cellular physiology and biochemistry》2006,18(1-3):67-74
Malfunction of the SLC26A4 protein leads to Pendred syndrome, characterized by sensorineural hearing loss, often associated with mild thyroid dysfunction and goiter. It is generally assumed that SLC26A4 acts as a chloride/anion exchanger, which in the thyroid gland transports iodide, and in the inner ear contributes to the conditioning of the endolymphatic fluid. Here we describe a fast fluorometric method able to be used to functionally scrutinize SLC26A4 and its mutants described in Pendred syndrome. The validation of the method was done by functionally characterizing the chloride/iodide transport of SLC26A4, and a mutant, i.e. SLC26A4(S28R), which we previously described in a patient with sensorineural hearing loss, hypothyroidism and goiter. Using the fluorometric method we describe here we can continuously monitor and quantify the iodide or chloride amounts transported by the cells, and we found that the transport capability of the SLC26A4(S28R) mutant protein is markedly reduced if compared to wild-type SLC26A4. 相似文献
13.
Jiandong Zhao Yongyi Yuan Shasha Huang Bangqing Huang Jing Cheng Dongyang Kang Guojian Wang Dongyi Han Pu Dai 《PloS one》2014,9(11)
Background
Nonsyndromic enlargement of vestibular aqueduct (NSEVA) is an autosomal recessive hearing loss disorder that is associated with mutations in SLC26A4. However, not all patients with NSEVA carry biallelic mutations in SLC26A4. A recent study proposed that single mutations in both SLC26A4 and KCNJ10 lead to digenic NSEVA. We examined whether KCNJ10 excert a role in the pathogenesis of NSEVA in Chinese patients.Methods
SLC26A4 was sequenced in 1056 Chinese patients with NSEVA. KCNJ10 was screened in 131 patients who lacked mutations in either one or both alleles of SLC26A4. Additionally, KCNJ10 was screened in 840 controls, including 563 patients diagnosed with NSEVA who carried biallelic SLC26A4 mutations, 48 patients with nonsyndromic hearing loss due to inner ear malformations that did not involve enlargement of the vestibular aqueduct (EVA), 96 patients with conductive hearing loss due to various causes, and 133 normal-hearing individuals with no family history of hereditary hearing loss.Results
925 NSEVA patients were found carrying two-allele pathogenic SLC26A4 mutations. The most frequently detected KCNJ10 mutation was c.812G>A (p.R271H). Compared with the normal-hearing control subjects, the occurrence rate of c.812G>A in NSEVA patients with lacking mutations in one or both alleles of SLC26A4 had no significant difference(1.53% vs. 5.30%, χ2 = 2.798, p = 0.172), which suggested that it is probably a nonpathogenic benign variant. KCNJ10 c.1042C>T (p.R348C), the reported EVA-related mutation, was not found in patients with NSEVA who lacked mutations in either one or both alleles of SLC26A4. Furthermore, the normal-hearing parents of patients with NSEVA having two SLC26A4 mutations carried the KCNJ10 c.1042C>T or c.812G>A mutation and a SLC26A4 pathogenic mutation.Conclusion
SLC26A4 is the major genetic cause in Chinese NSEVA patients, accounting for 87.59%. KCNJ10 may not be a contributor to NSEVA in Chinese population. Other genetic or environmental factors are possibly play a role in the etiology of Chinese EVA patients with zero or monoallelic SLC26A4 mutation. 相似文献14.
Pendrin and prestin both belong to a distinct anion transporter family called solute carrier protein 26A, or SLC26A. Pendrin (SLC26A4) is a chloride-iodide transporter that is found at the luminal membrane of follicular cells in the thyroid gland as well as in the endolymphatic duct and sac of the inner ear, whereas prestin (SLC26A5) is expressed in the plasma membrane of cochlear outer hair cells and functions as a unique voltage-dependent motor. We recently identified a motif that is critical for the motor function of prestin. We questioned whether it was possible to create a chimeric pendrin protein with motor capability by integrating this motility motif from prestin. The chimeric pendrin was constructed by substituting residues 160-179 in human pendrin with residues 156-169 from gerbil prestin. Non-linear capacitance and somatic motility, two hallmarks representing prestin function, were measured from chimeric pendrin-transfected human embryonic kidney 293 cells using the voltage clamp technique and photodiode-based displacement measurement system. We showed that this 14-amino acid substitution from prestin was able to confer pendrin with voltage-dependent motor capability despite the amino acid sequence disparity between pendrin and prestin. The molecular mechanism that facilitates motor function appeared to be the same as prestin because the motor activity depended on the concentration of intracellular chloride and was blocked by salicylate treatment. Radioisotope-labeled formate uptake measurements showed that the chimeric pendrin protein retained the capability to transport formate, suggesting that the gain of motor function was not at the expense of its inherent transport capability. Thus, the engineered pendrin was capable of both transporting anions and generating force. 相似文献
15.
Nofziger C Dossena S Suzuki S Izuhara K Paulmichl M 《Cellular physiology and biochemistry》2011,28(3):571-578
The expression and function of the anion exchanger pendrin (SLC26A4) was thought to be limited mainly to the inner ear, kidney and thyroid. Recent data indicates that pendrin is also expressed in the bronchial epithelium following exposure to the T(H)2-type cytokines, interleukin (IL)-4 and IL-13. Expression of the transporter is also upregulated in bronchial asthma and chronic obstructive pulmonary disease. Both diseases involve respiratory inflammation leading to tissue destruction/remodeling and decreased airway function, and data so far indicate that increased pendrin expression and/or activity might contribute to their pathogenesis. In this review, we summarize data that have emerged within the past years aimed at revealing the role for pendrin in the airway epithelia. 相似文献
16.
The pendrin (SLC26A4 or PDS) gene is responsible, when mutated, for the Pendred syndrome, a recessive disorder characterized by sensorineural hearing loss often accompanied by thyroid dysfunctions. Pendrin protein is an anion exchanger and we focused on a still unexplored function that it might play in view of its importance in the inner ear: Cl(-) fluxes regulation during cellular volume control. We challenged HEK-293 Phoenix cells over-expressing wild type pendrin (PDS HEK cells) together with the EYFP (Enhanced Yellow Fluorescent Protein) or over-expressing the EYFP alone (control HEK cells) with hypo-osmolar solutions. Taking advantage of the confocal optical sectioning we measured the cell volume. In addition, we determined the intracellular pH and chloride concentration with fluorescent probes (EYFP and seminaphthorhodafluor-5F, SNARF-5F). Consequently, we could estimate simultaneously Cl(-) fluxes, cellular volume and intracellular pH variations. Cl(-) movements markedly differed between PDS and control HEK cells upon hypotonic shock and are accompanied by an attenuation of the swelling induced pH drop in PDS HEK cells. The contemporary measurements of the three variables not yet reported in living cells, allowed to assess a possible influence of pendrin upregulation in volume homeostasis and evidenced its participation to Cl(-) fluxes. 相似文献
17.
18.
Pendred syndrome is an autosomal recessive disorder defined by sensorineural deafness, goiter and a partial organification defect of iodide. It is caused by biallelic mutations in the multifunctional anion transporter pendrin/SLC26A4. In human thyroid tissue, pendrin is localized at the apical membrane of thyroid follicular cells. The clinical phenotype of patients with Pendred syndrome and the fact that pendrin can mediate iodide efflux in transfected cells suggest that this anion exchanger may be involved in mediating iodide efflux into the follicular lumen, a key step in thyroid hormone biosynthesis. This concept has, however, been questioned. This review discusses supporting evidence as well as arguments questioning a role of pendrin in mediating iodide efflux in thyrocytes. 相似文献
19.
This paper presents the current views, regarding the pathomechanisms, which lead to the development of pathological symptoms in the enlargement of the vestibular aqueduct syndrome (EVAS) and the Pendred syndrome (PS). Associated phenotypes have been discussed and an attempt has been undertaken to correlate them with a corresponding genotype. Mutations of SLC26A4 gene are one of the factors, which are at the base of congenital hearing losses. Inherited hearing loss occurs in these cases either as an isolated phenomenon with anatomical anomalies of the labyrinth in the background (EVAS) or with endocrine disorders (PS). The official name of SLC26A4 gene is "solute carrier family 26, member 4". Pendrin, the product of its expression, transports iodine beyond thyroid follicular cells, where it is linked with thyroglobulin and, then, used in hormone synthesis. Abnormal expression of SLC26A4 gene results in disturbance of iodine organification. In the internal ear, pendrin transports bicarbonates to the endolymph, taking in this way an active part in pH control of the endolymph and providing proper functioning of KCNJ10 potassium channels and TRP5 calcium channels. Disorders of homeostasis in labyrinth fluids are responsible for abnormalities of its structure, such as enlargement of the vestibular aqueduct and of the endolymph sac. At present, the Human Gene Mutations database provides 124 recessive mutations of SLC26A4 gene. In EVAS and PS, two missense mutations are most frequently observed: L236P and T416P, as well as the mutation, regarding abnormal splicing process, i.e., IVS8+1G-A, in a total of 55% of the patients with recognised mutation of SLC26A4 gene; the remaining 45% of changes of this gene are unique mutations. 相似文献
20.
Reimold FR Heneghan JF Stewart AK Zelikovic I Vandorpe DH Shmukler BE Alper SL 《Cellular physiology and biochemistry》2011,28(3):435-450
SLC26A4/PDS mutations cause Pendred Syndrome and non-syndromic deafness. but some aspects of function and regulation of the SLC26A4 polypeptide gene product, pendrin, remain controversial or incompletely understood. We have therefore extended the functional analysis of wildtype and mutant pendrin in Xenopus oocytes, with studies of isotopic flux, electrophysiology, and protein localization. Pendrin mediated electroneutral, pH-insensitive, DIDS-insensitive anion exchange, with extracellular K((1/2)) (in mM) of 1.9 (Cl(-)), 1.8 (I(-)), and 0.9 (Br(-)). The unusual phenotype of Pendred Syndrome mutation E303Q (loss-of-function with normal surface expression) prompted systematic mutagenesis at position 303. Only mutant E303K exhibited loss-of-function unrescued by forced overexpression. Mutant E303C was insensitive to charge modification by methanethiosulfonates. The corresponding mutants SLC26A2 E336Q, SLC26A3 E293Q, and SLC26A6 E298Q exhibited similar loss-of-function phenotypes, with wildtype surface expression also documented for SLC26A2 E336Q. The strong inhibition of wildtype SLC26A2, SLC26A3, and SLC26A6 by phorbol ester contrasts with its modest inhibition of pendrin. Phorbol ester inhibition of SLC26A2, SLC26A3, and SLC26A6 was blocked by coexpressed kinase-dead PKCδ but was without effect on pendrin. Mutation of SLC26A2 serine residues conserved in PKCδ -sensitive SLC26 proteins but absent from pendrin failed to reduce PKCδ sensitivity of SLC26A2 (190). 相似文献