Biomedical subjects

M Li

Publications and source records attributed to M Li.

At least 505 records · Page 28Linked to original sources

PubMed1999

Connexins are expressed in primary brain tumors and enhance the bystander effect in gene therapy.

OBJECTIVE: Experimental brain tumor gene therapy with the herpes simplex virus thymidine kinase (HSV-tk) gene has demonstrated that not only HSV-tk transduced but surrounding non-HSV-tk transduced cells are killed when given ganciclovir. This so-called bystander effect has recently been shown to be dependent on connexin-mediated intercellular communication. To assess potential susceptibility to the bystander effect, we examined levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Connexin-26 expression has not previously been studied in primary brain tumors and connexin-43 expression has not been studied in nonastrocytic primary brain tumors. We also attempted to enhance the bystander effect in vitro by overexpressing connexin in tumor cells with high basal levels of connexin expression. METHODS: Western blot analysis and immunohistochemistry were used to determine levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Wild-type 9L gliosarcoma cells were transfected in vitro with the connexin-43 gene and the HSV-tk gene or the HSV-tk gene alone. The bystander effect of each transfectant was then assessed and compared. RESULTS: Most of the primary brain tumors tested, including low-grade astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, gangliogliomas, meningiomas, and medulloblastomas, showed connexin-26 and connexin-43 expression. Bystander experiments revealed a significant enhancement of the bystander effect in the gliosarcoma cells transfected with connexin-43 and HSV-tk, as compared with gliosarcoma cells transfected with HSV-tk alone. CONCLUSION: Most primary brain tumors express connexin-26 and connexin-43. This suggests that most primary brain tumors may be susceptible to the bystander effect of HSV-tk gene therapy. The bystander effect can be enhanced in vitro by overexpression of connexin-43 in a cell line with a high basal level of connexin-43 expression.

Animals↗

PubMed1999

Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene expression.

The human alcohol dehydrogenase 4 gene (ADH4) encodes the human pi-alcohol dehydrogenase (pi-ADH), which can contribute to ethanol metabolism at moderate and high concentrations of ethanol. There are no known structural variants of pi-ADH in humans. We report the first polymorphisms in the ADH4 gene, at three sites in the promoter: -192 bp, -159 bp and -75 bp, respectively. To determine whether these variations affected promoter function, different haplotypes of the ADH4 proximal promoter were subcloned into a luciferase reporter vector, and the relative promoter activity analysed in hepatoma cells. One of the three sites had a dramatic effect on promoter activity, while the others did not detectably affect activity. The -75A allele had promoter activity more than twice that of the -75C allele. Alcohol dehydrogenase activity is rate limiting for ethanol oxidation. We hypothesize that the different ADH4 alleles lead to different amounts of pi-ADH in liver, which affects the risk for alcoholism by modulating alcohol metabolism.

Alcohol Dehydrogenase↗

PubMed1999

Effects of training history on drug discrimination under concurrent fixed-interval schedules.

Pigeons with previous pentobarbital-discrimination training under concurrent VI 60 VI 240 and concurrent FI 60 FI 240 schedules were trained to respond under a concurrent FI 15 FI 285 schedule of food presentation. A second group of pigeons was trained only under the concurrent FI 15 FI 285 schedule. When responding stabilized during training sessions, both groups made 75-85% of their responses on the key where responses produced the reinforcer under the FI 15 component of the concurrent schedule. When the schedule was changed to concurrent FI 150 FI 150, the presence or absence of pentobarbital continued to control responding for the group with the extensive training history, but responding by the other group was rapidly controlled by the new reinforcement schedule. These data suggest that the behavioral history of the subject can be an important determinant of stimulus control by drugs. Despite these effects of training history on drug-discrimination responding, during the first minute of the session, the dose-response curves for pentobarbital, chlordiazepoxide, ethanol, phencyclidine and methamphetamine were similar in both groups of pigeons.

Animals↗

PubMed1999

Effects of drugs on responding under concurrent fixed-interval schedules and concurrent fixed-ratio schedules.

Pigeons were trained to respond under concurrent fixed-interval fixed-interval (concurrent FI FI) schedules with Fl values (in seconds) of 30/300, 60/240, 60/60, 240/60 and 300/30. A second group was trained to respond under concurrent fixed-ratio fixed-ratio (concurrent FR FR) with FR values of 10/40, 10/20, 20/20, 20/10 and 40/10. Under the concurrent Fl Fl schedules, pigeons responded much less often on the key with the higher reinforcement density than would be predicted basing on a perfect matching of the ratio of responses made to the ratio of reinforcers delivered, and the pigeons also showed a bias towards responding on the left key. Pentobarbital, methamphetamine, morphine and phencyclidine had little effect on bias, but high doses of methamphetamine, morphine and phencyclidine decreased undermatching. Under the concurrent FR FR schedules, pigeons responded almost entirely on the key with the higher reinforcement density. Only pentobarbital consistently disrupted this pattern of responding.

Animals↗

PubMed1999

Lack of difference between HAD and LAD rats in the stimulus generalization of ethanol to nicotine.

High alcohol drinking (HAD) and low alcohol drinking (LAD) rats were trained to discriminate 0.5 g/kg ethanol from saline. HAD and LAD rats learned the discrimination at the same rate and to the same level of asymptotic performance. In substitution tests, increasing doses of ethanol produced increased responding on the ethanol lever with dose-effect curves that were very similar in HAD and LAD rats. There was no generalization from ethanol to nicotine, or d-amphetamine, in either HAD or LAD rats. These data may be contrasted with data obtained with alcohol preferring rats (P rats) and alcohol non-preferring rats (NP rats), where the ethanol discrimination was learned more rapidly, asymptotic performance was better in P than in NP rats, and ethanol discriminative stimulus generalized to nicotine and partially to d-amphetamine in P, but not in NP rats. These data suggest that the differences in ethanol consumption reported previously by P and HAD rats relative to NP and LAD rats is not necessarily related to strain differences in ethanol discrimination as the differences in ethanol discrimination previously observed between P and NP rats do not occur in HAD and LAD rats.

Alcohol Drinking↗

PubMed1999

Linear viscoelasticity of hard sphere colloidal crystals from resonance detected with dynamic light scattering.

We present measurements of the high-frequency shear modulus and dynamic viscosity for nonaqueous hard sphere colloidal crystals both in normal and microgravity environments. All experiments were performed on a multipurpose PHaSE instrument. For the rheological measurements, we detect the resonant response to oscillatory forcing with a dynamic light scattering scheme. The resonant response for colloidal crystals formed in normal and microgravity environments was similar, indicating that the bulk rheological properties are unaffected by differing crystal structure and crystallite size within the experimental error. Our high-frequency shear modulus seems reasonable, lying close to Frenkel and Ladd's predictions [Phys. Rev. Lett. 59, 1169 (1987)] for the static modulus of hard sphere crystals. Our high-frequency dynamic viscosity, on the other hand, seems high, exceeding Shikata and Pearson [J. Rheol. 38, 601 (1994)] and van der Werff et al.'s measurements [Phys. Rev. A 39, 795 (1989)] on the high-frequency dynamic viscosity for metastable fluids. The measurements are in the linear regime for the shear modulus but may not be for the dynamic viscosity as Frith et al. [Powder Technol. 51, 27 (1987)] report that the dynamic viscosity passes through a maximum with strain amplitude.

Colloids↗

PubMed1999

Growth of (101) faces of tetragonal lysozyme crystals: determination of the growth mechanism.

Measurements of the macroscopic growth rates of the (101) face of tetragonal lysozyme crystals indicate an unusual dependence on the supersaturation [Forsythe et al. (1999), Acta Cryst. D55, 1005-1011] similar to that observed for the (110) face. As performed previously for the (110) face, the surface packing arrangement for the (101) face was constructed in this study based on earlier microscopic observations and theoretical analysis of the internal molecular packing. This allowed the minimum growth unit for this face to be identified as a tetramer corresponding to a single turn of helices centered about the 43 axes and the minimum growth step to be identified as of unimolecular height. A macroscopic mathematical model for the growth of the (101) face was developed based on the reversible formation of multimeric growth units in solution and the addition of a unit to the crystal face by dislocation and two-dimensional nucleation mechanisms. The calculations showed that the best fits were obtained for tetramer or octamer growth units in this model. This and other evidence suggests that while growth may proceed by a variety of growth units, the average size of these units is between that of a tetramer and an octamer.

Crystallization↗

PubMed1999

An analysis of breastfeeding patterns and menses returning in Chengdu, China.

OBJECTIVE: To study the relationship between infant feeding practices and the duration of lactational amenorrhea, WHO conducted a multi-centered prospective study in 7 countries from 1989. This paper reports the preliminary results based on the data collected in Chengdu center in China. METHODS: A detailed follow-up survey was conducted among 541 pairs of mothers and infants from delivery to the returning of menses of mothers at the interval of every 2 weeks. RESULTS: The results showed that the mean number of breastfeeding episodes and mean duration of breastfeeds had little correlation with the time since delivery. Within 6 months since delivery, the percentage of infants' feeds consisting of breastmilk was over 90%, and this percentage dropped to 70% at 1 year's age of infants. The time to the start of regular supplementation was 153 days postpartum. The proportion of women in exclusive breastfeeding at 2 weeks postpartum was 73.4%, and these figures at 3 and 6 months postpartum were about 60% and 40%, respectively. Until 18 months postpartum, nearly 80% mothers were partial breastfeeding their infants. The cumulative probabilities of menses returning were 0.0150, 0.0395, 0.2345 and 0.6820 at 61, 89, 187 and 369 days postpartum respectively. The median duration of lactational amenorrhea was 282 days. CONCLUSION: These results indicated that the duration of lactational amenorrhea would be prolonged if the time of exclusive/predominant breastfeed was extended and the supplementary food was introduced later. The paper concluded that the first menses returning was the signal for initiating contraceptive methods for women.

Adult↗

PubMed1999

Cloning and sequencing of the genes downstream of the wbf gene cluster of Vibrio cholerae serogroup O139 and analysis of the junction genes in other serogroups.

The DNA sequence of the O-antigen biosynthesis cluster (wbf) of a recently emergent pathogen, Vibrio cholerae serogroup O139, has been determined. Here we report the sequence of the genes downstream of the O139 wbfX gene and analysis of the genes flanking the wbf gene cluster in other serogroups. The gene downstream of wbfX, designated rjg (right junction gene), is predicted to be not required for O-antigen biosynthesis but appears to be a hot spot for DNA rearrangements. Several variants of the rjg gene (three different insertions and a deletion) have been found in other serogroups. DNA dot blot analysis of 106 V. cholerae strains showed the presence of the left and right junction genes, gmhD and rjg, respectively, in all strains. Further, these genes mapped to a single I-CeuI fragment in all 21 strains analyzed by pulsed-field gel electrophoresis, indicating a close linkage. The insertion sequence element IS1358, found in both O1 and O139 wb* regions, is present in 61% of the strains tested; interestingly, where present, it is predominantly linked to the wb* region. These results indicated a cassette-like organization of the wb* region, with the conserved genes (gmhD and rjg) flanking the divergent, serogroup-specific wb* genes and IS1358. A similar organization of the wb* region in other serogroups raises the possibility of the emergence of new pathogens by homologous recombination via the junction genes.

Amino Acid Sequence↗

PubMed1999

Sequence and insertion sites of murine melanoma-associated retrovirus.

We previously showed that B16 melanoma cells produce ecotropic melanoma-associated retrovirus (MelARV) which encodes a melanoma-associated antigen recognized by MM2-9B6 monoclonal antibody. The biological significance of MelARV in melanoma formation remains unknown. We found that infection of normal melanocytes with MelARV resulted in malignant transformation. It is likely that MelARV emerged from the defective Emv-2 provirus, a single copy of ecotropic provirus existing in the genome of C57BL/6 mice. In the present study, we cloned and sequenced the full-length MelARV genome and its insertion sites and we completed sequencing of the Emv-2 provirus. Our data show that MelARV has a typical full-length retroviral genome with high homology (98.54%) to Emv-2, indicating a close relationship between both viruses. MelARV probably emerged as a result of recombination between Emv-2 and an endogenous nonecotropic provirus. Some observed differences in the gag and pol regions of MelARV might account for the restoration of productivity and infectivity of a novel retrovirus that somatically emerged during melanoma formation. MelARV does not contain any oncogene and therefore might induce transformation by insertional mutagenesis. We sequenced two insertion sites of MelARV. The first insertion site represents the 3' coding region of the c-maf proto-oncogene at 67.0 centimorgans (cM) on chromosome 8. The c-maf proto-oncogene encodes a basic leucine zipper protein homologous to c-fos and c-jun. Insertion of MelARV in BL6 melanoma cells resulted in the up-regulation of c-maf. It is noteworthy that the Emv-2 provirus is also inserted into a noncoding region at 61.0 cM on the same chromosome 8. The second insertion site is the 3' noncoding region of the DNA polymerase gamma (PolG) gene on chromosome 7. The expression of PolG was not affected by the MelARV insertion. Further investigation of the biological significance of MelARV in melanoma formation is being undertaken.

Animals↗

PubMed1999

Identification and characterization of Kaposi's sarcoma-associated herpesvirus K8.1 virion glycoprotein.

Kaposi's sarcoma-associated herpesvirus (KSHV) has been consistently identified in Kaposi's sarcomas (KS), body cavity-based lymphomas (BCBL), and some forms of Castleman's disease. Previous serological tests with KS patient sera have detected lytic-cycle polypeptides from KSHV-infected BCBL cells. We have found that these polypeptides are predominantly encoded by the K8.1 open reading frame, which is present in the same genomic position as virion envelope glycoproteins of other gammaherpesviruses. The cDNA of K8.1 from BCBL-1 cells was found to encode a glycosylated protein with an apparent molecular mass of 37 kDa. K8.1 was found to be expressed during lytic KSHV replication in BCBL-1 cells and was localized on the surface of cells and virions. The results of immunofluorescence and immunoelectron microscopy suggest that KSHV acquires K8.1 protein on its virion surface during the process of budding at the plasma cell membrane. When KSHV K8.1 derived from mammalian cells was used as an antigen in immunoblot tests, antibodies to K8.1 were detected in 18 of 20 KS patients and in 0 of 10 KS-negative control subjects. These results demonstrate that the K8.1 gene encodes a KSHV virion-associated glycoprotein and suggest that antibodies to K8.1 may prove useful as contributory serological markers for infection by KSHV.

Amino Acid Sequence↗

PubMed1999

Role of cellular tumor necrosis factor receptor-associated factors in NF-kappaB activation and lymphocyte transformation by herpesvirus Saimiri STP.

The STP oncoproteins of the herpesvirus saimiri (HVS) subgroup A strain 11 and subgroup C strain 488 are now found to be stably associated with tumor necrosis factor receptor-associated factor (TRAF) 1, 2, or 3. Mutational analyses identified residues of PXQXT/S in STP-A11 as critical for TRAF association. In addition, a somewhat divergent region of STP-C488 is critical for TRAF association. Mutational analysis also revealed that STP-C488 induced NF-kappaB activation that was correlated with its ability to associate with TRAFs. The HVS STP-C488 P10-->R mutant was deficient in human T-lymphocyte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo. The STP-C488 P10-->R mutant was also defective in Rat-1 fibroblast transformation, and fibroblast cell transformation was blocked by a TRAF2 dominant-negative mutant. These data implicate TRAFs in STP-C488-mediated transformation of human lymphocytes and rodent fibroblasts. Other factors are implicated in immortalization of common marmoset T lymphocytes and may also be critical in the transformation of human lymphocytes and rodent fibroblasts.

Amino Acid Sequence↗

PubMed1999

Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys.

Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus that is most closely related to the human Kaposi's sarcoma-associated herpesvirus (KSHV). We have identified a distinct open reading frame at the left end of RRV and designated it R1. The position of the R1 gene is equivalent to that of the saimiri transforming protein (STP) of herpesvirus saimiri (HVS) and of K1 of KSHV, other members of the gamma-2 or rhadinovirus subgroup of herpesviruses. The R1 sequence revealed an open reading frame encoding a product of 423 amino acids that was predicted to contain an extracellular domain, a transmembrane domain, and a C-terminal cytoplasmic tail reflective of a type I membrane-bound protein. The predicted structural motifs of R1, including the presence of immunoreceptor tyrosine-based activation motifs, resembled those in K1 of KSHV but were distinct from those of STP. R1 sequences from four independent isolates from three different macaque species revealed 0.95 to 7.3% divergence over the 423 amino acids. Variation was located predominantly within the predicted extracellular domain. The R1 protein migrated at 70 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was extensively glycosylated. Tagged R1 protein was localized to the cytoplasmic and plasma membranes of transfected cells. Expression of the R1 gene in Rat-1 fibroblasts induced morphologic changes and focus formation, and injection of R1-expressing cells into nude mice induced the formation of multifocal tumors. A recombinant herpesvirus in which the STP oncogene of HVS was replaced by R1 immortalized T lymphocytes to interleukin-2-independent growth. These results indicate that R1 is an oncogene of RRV.

Amino Acid Sequence↗

PubMed1999

Axonal and perikaryal involvement in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: To assess the extent of loss of myelinated nerve fibres and spinal motor neuron loss in chronic inflammatory demyelinating polyneuropathy (CIDP), a clinicopathological study was conducted on biopsied sural nerves and necropsied spinal cords from patients with CIDP. METHODS: The myelinated fibre pathology of 71 biopsied sural nerves and motor neuron pathology of nine necropsied spinal cords at L4 levels in patients with CIDP were quantitatively and immunohistochemically assessed. RESULTS: Myelinated nerve fibre density was significantly diminished to 65.4% of the control values (p <0.0001), correlating inversely with the extent of segmental demyelination and remyelination (r = -0.43, p < 0.0005) and duration of illness (r = -0.31, p < 0.01). Numbers of large spinal motor neurons in CIDP were variably but significantly diminished (range from 46.0 to 97.6% of the age matched control value (p < 0.005)), and reactive astrogliosis was evident in the ventral horn in CIDP. The frequency of ventral horn neurons exhibiting central chromatolysis and the accumulation of phosphorylated high molecular weight neurofilament protein was significantly higher in CIDP than in controls (p<0.01 and p<0.05). CONCLUSIONS: The loss of nerve axons and spinal motor neurons is common in CIDP, and extensive in some cases. These neuronal and axonal losses may influence the functional prognosis in CIDP.

Adolescent↗

PubMed1999

Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis.

The nuclear phosphoprotein p53 acts as a transcription factor and is involved in growth inhibition and apoptosis. The present study was designed to examine the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum in the presence or absence of alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and spermine in DFMO-treated cells decreased dramatically at 4 days and remained depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant increase in expression of the p53 gene. The p53 mRNA levels increased 4 days after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by increases in p53 protein. Polyamines given together with DFMO completely prevented increased expression of the p53 gene. Increased expression of the p53 gene in DFMO-treated cells was associated with a significant increase in G1 phase growth arrest. In contrast, no features of programmmed cell death were identified after polyamine depletion: no internucleosomal DNA fragmentation was observed, and no morphological features of apoptosis were evident in cells exposed to DFMO for 4, 6, and 12 days. These results indicate that 1) decreasing cellular polyamines increases expression of the p53 gene and 2) activation of p53 gene expression after polyamine depletion does not induce apoptosis in intestinal crypt cells. These findings suggest that increased expression of the p53 gene may play an important role in growth inhibition caused by polyamine depletion.

Animals↗

PubMed1999

Voltage-sensitive calcium currents are acutely increased by nerve growth factor in PC12 cells.

Whole cell calcium currents were recorded from PC12 cells with the perforated patch technique. Currents were evoked by step depolarization from a holding potential of -90 mV. Nerve growth factor (NGF) increased calcium currents through L-type calcium channels by >75% within 3-5 min. This increase was inhibited by K-252a, by nifedipine, and by inhibition or down-regulation of kinase C. Brain-derived neurotrophic factor (BDNF) also increased calcium current, but to a smaller extent. Thus increases in calcium current can be linked to activation of either the high- or the low-affinity nerve growth factor receptor. Increases in presynaptic calcium uptake appear to be a crucial element in the short-term actions of the neurotrophins on neurotransmitter release leading to long-term potentiation. Also, the control of calcium uptake is likely to be an important factor in the long-term actions of the neurotrophins on neuronal survival and neuronal protection. The present data indicate that the PC12 cell may be a useful model for studying the effect of the neurotrophins on calcium uptake.

Animals↗

PubMed1999

Prohormone convertases 1 and 2 process ProPACAP and generate matured, bioactive PACAP38 and PACAP27 in transfected rat pituitary GH4C1 cells.

Pituitary adenylate cyclase-activating polypetide (PACAP) exists in two amidated forms, PACAP38 and PACAP27, which are expressed in the magnocellular and parvocellular neurons of the paraventricular nucleus (PVN) and the magnocellular neurons of the supraoptic nucleus (SON) of the hypothalamus. The prohormone convertases PC1 and PC2, subtilisin-like PCs of the Kex2 family, are expressed in neuroendocrine cells. Immunocytochemistry and in situ hybridization of PC1 and PC2 in the hypothalamus have shown that PC1 and PC2 are also present in the PVN and SON. Therefore, it is possible that the precursor of PACAP is processed by PC1 and/or PC2 in the hypothalamic nuclei and then converted to its mature forms. To test this hypothesis, rat pituitary GH4C1 cells were supertransfected with human PACAP cDNA and either rat PC1 or PC2 cDNA. The acid extracts of these cells were analyzed by reversed-phase HPLC for proPACAP, PACAP38 and/or PACAP27 radioimmunoassays using three antibodies with different recognition sites, and then bioassayed for the ability to stimulate adenylate cyclase. The cells transfected with PACAP cDNA alone yielded PACAP-like immunoreactivity (PACAP-li) corresponding to molecular weights between 15 and 20 kDa without PACAP bioactivity. Cotransfection of these cells with PC1 or PC2 generated PACAP-li, which coeluted with synthetic PACAP38 and PACAP27, respectively. Western blot also revealed 4.5- and 3.0-kDa PACAP-li bands, which correspond to the molecular weights of PACAP38 and PACAP27, respectively. The HPLC fractions containing PACAP-li, which were coeluted with synthetic PACAP38 and PACAP27, showed marked bioactivities. These findings suggest that the precursor of PACAP expressed in the PVN and SON of the hypothalamus could be efficiently processed by PC1 and PC2, and then converted to mature, bioactive PACAP38 and PACAP27.

Animals↗

PubMed1999

A PDZ-interacting domain in CFTR is an apical membrane polarization signal.

Polarization of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, to the apical plasma membrane of epithelial cells is critical for vectorial transport of chloride in a variety of epithelia, including the airway, pancreas, intestine, and kidney. However, the motifs that localize CFTR to the apical membrane are unknown. We report that the last 3 amino acids in the COOH-terminus of CFTR (T-R-L) comprise a PDZ-interacting domain that is required for the polarization of CFTR to the apical plasma membrane in human airway and kidney epithelial cells. In addition, the CFTR mutant, S1455X, which lacks the 26 COOH-terminal amino acids, including the PDZ-interacting domain, is mispolarized to the lateral membrane. We also demonstrate that CFTR binds to ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50), an apical membrane PDZ domain-containing protein. We propose that COOH-terminal deletions of CFTR, which represent about 10% of CFTR mutations, result in defective vectorial chloride transport, partly by altering the polarized distribution of CFTR in epithelial cells. Moreover, our data demonstrate that PDZ-interacting domains and PDZ domain-containing proteins play a key role in the apical polarization of ion channels in epithelial cells.

Amino Acid Sequence↗