A Wayne Vogl

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (104)337.03 Total impact

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    ABSTRACT: Francisella novicida is a surrogate pathogen commonly used to study infections by the potential bioterrorism agent, Francisella tularensis. One of the primary sites of Francisella infections is the liver where >90 % of infected cells are hepatocytes. It is known that once Francisella enter cells it occupies a membrane-bound compartment, the Francisella-containing vacuole (FCV), from which it rapidly escapes to replicate in the cytosol. Recent work examining the Francisella disulfide bond formation (Dsb) proteins, FipA and FipB, have demonstrated that these proteins are important during the Francisella infection process; however, details as to how the infections are altered in epithelial cells have remained elusive. To identify the stage of the infections where these Dsbs might act during epithelial infections, we exploited a hepatocyte F. novicida infection model that we recently developed. We found that F. novicida ΔfipA-infected hepatocytes contained bacteria clustered within lysosome-associated membrane protein 1-positive FCVs, suggesting that FipA is involved in the escape of F. novicida from its vacuole. Our morphological evidence provides a tangible link as to how Dsb FipA can influence Francisella infections.
    Cell and Tissue Research 08/2015; DOI:10.1007/s00441-015-2246-0 · 3.57 Impact Factor
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    ABSTRACT: The mechanical properties of aortic elastin vary regionally, but the microstructural basis for this variation is unknown. This study was designed to identify the relative contributions of lamellar and interlamellar elastin to circumferential load bearing in the mouse thoracic and abdominal aortas. Forces developed in uniaxial tests of samples of fresh and autoclaved aorta were correlated with elastin content and morphology obtained from histology and multiphoton laser scanning microscopy. Autoclaving should render much of the interlamellar elastin mechanically incompetent. In autoclaved tissue force per unit sample width correlated with lamellar elastin content (P≪0.001) but not total elastin content. In fresh tissue at low strain where elastin dominates the mechanical response, forces were higher than in the autoclaved tissue, but force did not correlate with total elastin content. Therefore although interlamellar elastin likely contributed to the stiffness in the fresh aorta, its contribution appeared not in proportion to its quantity. In both fresh and autoclaved tissue, elastin stiffness consistently decreased along the abdominal aorta, a key area for aneurysm development, and this difference could not be fully accounted for on the basis of either lamellar or total elastin content. These findings are relevant to the development of mathematical models of arterial mechanics, particularly for mouse models of arterial diseases involving elastic tissue. In microstructural based models the quantity of each mural constituent determines its contribution to the total response. This study shows elastin's mechanical response cannot necessarily be accounted for on the basis of fibre quantity, orientation, and modulus. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Biomechanics 08/2015; DOI:10.1016/j.jbiomech.2015.08.004 · 2.75 Impact Factor
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    Canadian Journal of Zoology 07/2015; DOI:10.1139/cjz-2014-0311 · 1.30 Impact Factor
  • Kevin R B Lyon · Emy Bosseboeuf · A Wayne Vogl
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    ABSTRACT: Tubulobulbar complexes (TBCs) are elongate subcellular machines responsible for internalizing intercellular junctions during sperm release. Each complex consists of a double membrane tubular core terminating in a clathrin-coated pit. The core is surrounded by a network of actin filaments and a distinct swelling or bulb, that lacks an association with actin, develops in the distal third of the structure. The bulb eventually buds from the complex and enters endocytic compartments of the Sertoli cell. The relationship of the actin cuff to the formation and budding of the bulb is not known. To gain insight into this relationship, we perturbed the actin networks of TBCs with cytochalasin D. When isolated testes were perfused with a physiological buffer containing cytochalasin D, apical TBCs at stage VII of spermatogenesis were associated with lower levels of actin compared to controls. At the ultrastructural level, the actin networks in cytochalasin D-treated testes appeared patchy, and ectopic bulbs and swollen tubular regions occurred. When normal untreated samples at early stage VII were analyzed, large elongate bulbs and short tubular sections were observed. Together, these results suggest a new model for TBC vesiculation in which the actin network begins to disassemble and the tubular region begins to swell into a bulb. As actin disassembly continues, the coated pit and most of the tubular region is incorporated into the enlarging bulb. The remaining short neck of the bulb near the base of the complex undergoes scission, and the bulb is internalized. Copyright 2015 by The Society for the Study of Reproduction.
    Biology of Reproduction 06/2015; 93(1). DOI:10.1095/biolreprod.115.128942 · 3.32 Impact Factor
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    ABSTRACT: Rorqual whales (Balaenopteridae) are among the largest vertebrates that have ever lived and include blue (Balaenoptera musculus) and fin (Balaenoptera physalus) whales. Rorquals differ from other baleen whales (Mysticeti) in possessing longitudinal furrows or grooves in the ventral skin that extend from the mouth to the umbilicus. This ventral grooved blubber directly relates to their intermittent lunge feeding strategy, which is unique among vertebrates and was potentially an evolutionary innovation that led to gigantism in this lineage [1]. This strategy involves the rorqual whale rapidly engulfing a huge volume of prey-laden water and then concentrating the prey by more slowly expelling the water through baleen plates (Figure 1A). The volume of water engulfed during a lunge can exceed the volume of the whale itself [2]. During engulfment, the whale accelerates, opens its jaw until it is almost perpendicular to the rostrum, and then the highly compliant floor of the oral cavity is inflated by the incoming water [3]. The floor of the oral cavity expands by inversion of the tongue and ballooning of the adjacent floor of the mouth into the cavum ventrale, an immense fascial pocket between the body wall and overlying blubber layer that reaches as far back as the umbilicus. The ventral grooved blubber in fin whales expands by an estimated 162% in the circumferential direction and 38% longitudinally [4]. In fin whales, multiple lunges can occur during a single dive, and the average time between lunges is just over forty seconds [3]. Here, we show that nerves in the floor of the oral cavity of fin whales are highly extensible. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Current Biology 04/2015; 25(9):345-361. DOI:10.1016/j.cub.2015.03.007 · 9.57 Impact Factor
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    ABSTRACT: There is a growing body of evidence that exposure to endocrine disrupting chemicals and to estrogenic compounds in particular can affect the testis and male fertility. In the present study, the constitutive expression of steroidogenic and non-steroidogenic cytochrome P450 (CYP) and related enzymes in adult rat testis, and their regulation by estradiol and bisphenol A, were investigated. CYP1B1, CYP2A1, NADPH-cytochrome P450 oxidoreductase (POR) and microsomal epoxide hydrolase (mEH) proteins, together with CYP17A1 and 3β-hydroxysteroid dehydrogenase (3HSD), were detected by immunoblot analysis in testicular microsomes prepared from untreated adult Sprague-Dawley rats. In contrast, CYP1A, CYP2B, CYP2E, CYP2D, CYP2C, CYP3A and CYP4A enzymes were not detected. Immunofluorescence staining of cryosections of perfusion-fixed testes showed that CYP1B1, CYP2A1, CYP17A1 and 3HSD were expressed exclusively or mainly in interstitial cells, whereas mEH and POR protein staining was detected both in interstitial cells and in seminiferous tubules. Testicular CYP1B1 and CYP2A1 protein levels were decreased following treatment of adult rats with estradiol benzoate at 0.004, 0.04, 0.4 or 4 μmol/kg/day or bisphenol A at 400 or 800 μmol/kg/day, for 14 days, whereas expression of 3HSD was unaffected. Testicular CYP17A1, POR and mEH protein expression was also down-regulated at the three highest dosages of estradiol benzoate and at both dosages of bisphenol A. The present study is the first to establish the cellular localization of CYP1B1, mEH and POR in rat testis and to demonstrate the suppressive effect of bisphenol A on testicular CYP1B1, CYP2A1, mEH and POR protein levels.
    Toxicological Sciences 04/2014; 140(1). DOI:10.1093/toxsci/kfu070 · 3.85 Impact Factor
  • A Wayne Vogl · Min Du · Elsie Wang · J'nelle S Young
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    ABSTRACT: Tubulobulbar complexes are elaborate clathrin/actin related structures that form at sites of intercellular attachment in the seminiferous epithelium of the mammalian testis. Here we summarize what is currently known about the morphology and molecular composition of these structures and review evidence that the structures internalize intercellular junctions both at apical sites of Sertoli cell attachment to spermatids, and at basal sites where Sertoli cells form the blood-testis barrier. We present updated models of the sperm release and spermatocyte translocation mechanisms that incorporate tubulobulbar complexes into their designs.
    Seminars in Cell and Developmental Biology 11/2013; 30. DOI:10.1016/j.semcdb.2013.11.002 · 6.27 Impact Factor
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    ABSTRACT: The mouse protein phosphatase gene Ppp1cc is essential for male fertility, with mutants displaying a failure in spermatogenesis including a widespread loss of post-meiotic germ cells and abnormalities in the mitochondrial sheath. This phenotype is hypothesized to be attributed to the loss of the testis specific isoform PPP1CC2. To identify PPP1CC2 interacting proteins with a function in spermatogenesis, we performed GST pull down assays in mouse testis lysate. Amongst the identified candidate interactors was the testis specific protein kinase TSSK1, which is also essential for male fertility. Subsequent interaction experiments have confirmed the capability of PPP1CC2 to form a complex with TSSK1 mediated by direct interaction of each with the kinase substrate protein TSKS. Interaction between PPP1CC2 and TSKS is mediated through an RVxF docking motif on the TSKS surface. Phosphoproteomic analysis of the mouse testis identified a novel serine phosphorylation site within the TSKS RVxF motif that appears to negatively regulate binding to PPP1CC2. Immunohistochemical analysis of TSSK1 and TSKS in Ppp1cc mutant testis showed reduced accumulation to distinct cytoplasmic foci and other abnormalities in their distribution consistent with the loss of germ cells and seminiferous tubule disorganization observed in the Ppp1cc mutant phenotype. A comparison of Ppp1cc and Tssk1/2 knockout phenotypes via electron microscopy revealed similar abnormalities in the morphology of the mitochondrial sheath. This data demonstrates a novel kinase/phosphatase complex in the testis that could play a critical role in the completion of spermatogenesis.
    Reproduction 10/2013; 147(1). DOI:10.1530/REP-13-0224 · 3.17 Impact Factor
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    ABSTRACT: Fin whales have an incompliant aorta, which, we hypothesize, represents an adaptation to large, depth-induced variations in arterial transmural pressures. We hypothesize these variations arise from a limited ability of tissues to respond to rapid changes in ambient ocean pressures during a dive. We tested this hypothesis by measuring arterial mechanics experimentally and modelling arterial transmural pressures mathematically. The mechanical properties of mammalian arteries reflect the physiological loads they experience, so we examined a wide range of fin whale arteries. All arteries had abundant adventitial collagen that was usually recruited at very low stretches and inflation pressures (2-3 kPa), making arterial diameter largely independent of transmural pressure. Arteries withstood significant negative transmural pressures (-7 to -50 kPa) before collapsing. Collapse was resisted by recruitment of adventitial collagen at very low stretches. These findings are compatible with the hypothesis of depth-induced variation of arterial transmural pressure. Because transmural pressures depend on thoracic pressures, we modelled the thorax of a diving fin whale to assess the likelihood of significant variation in transmural pressures. The model predicted that deformation of the thorax body wall and diaphragm could not always equalize thoracic and ambient pressures because of asymmetrical conditions on dive descent and ascent. Redistribution of blood could partially compensate for asymmetrical conditions, but inertial and viscoelastic lag necessarily limits tissue response rates. Without pressure equilibrium, particularly when ambient pressures change rapidly, internal pressure gradients will develop and expose arteries to transient pressure fluctuations, but with minimal hemodynamic consequence due to their low compliance.
    Journal of Experimental Biology 07/2013; 216(Pt 14):2548-2563. DOI:10.1242/jeb.081802 · 2.90 Impact Factor
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    ABSTRACT: From puberty and throughout adult spermatogenesis, retinoid signalling is essential for germ cell differentiation and male fertility. The initiation of spermatogonial differentiation and germ cell meiosis occurs under the direction of local retinoid signalling in the testis, and corresponds with the final phase of somatic Sertoli cell differentiation at puberty. Here, we consider the cellular and molecular basis of retinoid actions upon Sertoli cell differentiation. Primary rat Sertoli cells were isolated during the pubertal proliferative and quiescent phases at postnatal days 10- and 20- respectively, and cultured with all-trans-retinoic acid. We show that retinoid signalling can potently suppress activin-induced proliferation by antagonising G1 phase progression and entry into the cell cycle. Retinoid signalling was also found to initiate tight junction formation in primary Sertoli cells, consistent with a pro-differentiative role. This study implicates retinoid signalling in the differentiation of both somatic and germ cells in the testis at puberty.
    Molecular and Cellular Endocrinology 07/2013; 377(1-2). DOI:10.1016/j.mce.2013.06.034 · 4.41 Impact Factor
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    ABSTRACT: Tubulobulbar complexes (TBCs) are actin-related endocytic structures that internalize intercellular junctions in the seminiferous epithelium. The structures consist of elongate tubular projections of the attached plasma membranes of two adjacent cells that project into Sertoli cells. This double membrane core is cuffed by a dentritic actin network and is capped at its end by a clathrin-coated pit. Here we explore the possibility that elements of the spectrin cytoskeleton are associated with clusters of tubulobulbar complexes that develop at adhesion junctions between late spermatids and Sertoli cells at the apex of the epithelium, and extend what is known about the distribution of plectin at the sites. Cryo-sections of perfusion-fixed testes and apical processes of Sertoli cells mechanically dissociated from perfusion-fixed testes were probed for spectrin, EPB41, and actin and analyzed using conventional fluorescence microscopy and confocal microscopy. Data sets from confocal microscopy were analyzed further in three-dimensional reconstructions using computer software. Additional apical Sertoli cell processes were probed for plectin and analyzed using conventional fluorescence microscopy. Antibodies generated against elements of the spectrin cytoskeleton react with material around and between the actin cuffs of tubulobulbar complexes, but appear excluded from the actin cuffs themselves. A similar staining pattern occurs with a probe for plectin. Immunoelectron microscopy confirmed the staining patterns observed by fluourescence microscopy. Based on our results, we suggest that a network of spectrin and plectin forms a scaffold around tubulobulbar complexes that may provide support for the actin network that cuffs each complex and also link adjacent complexes together.
    07/2013; 3(3):e25733. DOI:10.4161/spmg.25733
  • 46th Annual Meeting of the Society for the Study of Reproduction, Montreal, Canada; 07/2013
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    ABSTRACT: http://www.fasebj.org/cgi/content/meeting_abstract/27/1_MeetingAbstracts/523.2
    FASEB Meeting; 04/2013
  • Ni Lan · A Wayne Vogl · Joanne Weinberg
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    ABSTRACT: Background: During late prenatal and early postnatal life, the reproductive system in males undergoes an extensive series of physiological and morphological changes. Prenatal ethanol (EtOH) exposure has marked effects on the development of the reproductive system, with long-term effects on function in adulthood. The present study tested the hypothesis that prenatal EtOH exposure will delay the onset of spermatogenesis. Methods: Development of the seminiferous tubules and the onset of spermatogenesis were examined utilizing a rat model of fetal alcohol spectrum disorder (FASD). Male offspring from ad libitum-fed control (C), pair-fed (PF), and EtOH-fed (prenatal alcohol exposure [PAE]) dams were terminated on postnatal (PN) days 5, 15, 18, 20, 25, 35, 45, and 55, to investigate morphological changes through morphometric analysis of the testes from early neonatal life through young adulthood. Results: PAE males had lower relative (adjusted for body weight) testis weights compared with PF and/or C males from PN15 through puberty (PN45). In addition, fewer gonocytes (primordial germ cells) were located on the basal lamina on PN5, while more of those touching the basal lamina were dividing in PAE compared with PF and C males, suggesting delayed cell division and migration processes. As well, the percentage of tubules with open lumena was lower in PAE compared with PF and C males on PN18 and 20, and PAE males had fewer primary spermatocytes per tubule on PN18 and round spermatids per tubule on PN25 compared with C males. Finally, the percentage of tubules at stages VII and VIII, when mature spermatids move to the apex of the epithelium and are released, was lower in PAE compared with PF and/or C males in young adulthood (PN55). Conclusions: Maternal EtOH consumption appears to delay both reproductive development and the onset of spermatogenesis in male offspring, with effects persisting at least until young adulthood.
    Alcoholism Clinical and Experimental Research 03/2013; 37(7). DOI:10.1111/acer.12079 · 3.21 Impact Factor
  • A Wayne Vogl · J'nelle S Young · Min Du
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    ABSTRACT: Tubulobulbar complexes are actin-filament-related structures that form at intercellular junctions in the seminiferous epithelium of mammalian testis. The structures occur both at adhesion junctions between Sertoli cells and the maturing spermatids in apical regions of the epithelium, and at junction complexes between neighboring Sertoli cells near the base of the epithelium. Here, we review the general morphology and molecular composition of tubulobulbar complexes, and also include a description of tubulobulbar complex structure in the human seminiferous epithelium. Although tubulobulbar complexes are unique to the seminiferous epithelium, they have the molecular signature of clathrin-based endocytosis machinery present generally in cells. We review the evidence that tubulobulbar complexes internalize intact intercellular junctions and are significant components of the sperm-release mechanism and the process by which spermatocytes translocate from basal to adluminal compartments of the epithelium.
    International review of cell and molecular biology 02/2013; 303:319-55. DOI:10.1016/B978-0-12-407697-6.00008-8 · 3.42 Impact Factor
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    ABSTRACT: During metastatic progression, an aberrant epithelial-to-mesenchymal transformation (EMT) that is most often driven by the loss of the cell-cell adhesion molecule E-cadherin generates non-cohesive tumor cells that are highly invasive. We used mesenchymally-transformed, E-cadherin negative MDA-MB-231 breast carcinoma cells in a natural product screen and determined that the triterpenoid saponin sarasinoside A1 inhibited their invasion and the invasion of a number of other tumor cell lines. Sarasinoside A1 also caused MDA-MB-231 cells to become cohesive in 3-dimensional basement membrane and collagen gel cultures. In 2-dimensional culture, sarasinoside A1 initiated a morphologic re-epithelialization of MDA-MB-231 cells wherein pre-existing non-epithelial cadherins and the junction-associated proteins β-catenin and ZO-1 all re-localized to sites of cell-cell contact. Additionally, the intercellular space between neighboring cells narrowed considerably, the stability of polymerized actin at cell-cell contact sites increased, and there was a recruitment and stabilization of nectin-based adhesion complexes to these sites, all of which strongly suggested that functional cell-cell junctions had formed. Importantly, sarasinoside A1 induced nascent cell-cell junction formation that did not require changes in gene expression and was not associated with an induction of E-cadherin, but resulted in increased activation of Rap GTPases. Therefore, our findings with sarasinoside A1 suggest that it may be possible to re-epithelialize metastatic tumor cells with phenotypic consequence even when E-cadherin is completely absent.
    Molecular Cancer Research 02/2013; 11(5). DOI:10.1158/1541-7786.MCR-12-0385 · 4.38 Impact Factor
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    ABSTRACT: Tubulobulbar complexes are cytoskeleton-related membrane structures that develop at sites of intercellular attachment in the mammalian seminiferous epithelium. At apical junctions between Sertoli cells and spermatids the structures internalize adhesion junctions and are a component of the sperm release mechanism. Here we explore the possibility that tubulobulbar complexes that form at the "blood-testis barrier" are sub-cellular machines that internalize basal junction complexes. Using electron microscopy we confirm that morphologically identifiable tight and gap junctions are present in basal tubulobulbar complexes in rats. In addition, immunological probes for claudin-11 (CLDN11), connexin-43 (GJA1), and nectin-2 (PVRL2) react with linear structures at the light level that we interpret as tubulobulbar complexes, and probes for early endosome antigen 1 (EEA1) and Rab5 (RAB5A) react in similar locations. Significantly, fluorescence patterns for actin and claudin-11 indicate that the amount of junction present is dramatically reduced over the time period that tubulobulbar complexes are known to be most prevalent during spermatogenesis. We also demonstrate, using electron microscopy and fluorescence microscopy, that tubulobulbar complexes develop at basal junctions in primary cultures of Sertoli cells, and that like their in vivo counterparts, the structures contain junction proteins. We use this culture system together with transfection techniques to show that junction proteins from one transfected cell occur in structures that project into adjacent non-transfected cells as predicted by the junction internalization hypothesis. On the basis of our findings we present a new model for basal junction remodeling as it relates to spermatocyte translocation in the seminiferous epithelium.
    Biology of Reproduction 01/2013; 88(3). DOI:10.1095/biolreprod.112.104851 · 3.32 Impact Factor
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    ABSTRACT: We have identified cpna-1 (F31D5.3) as a novel essential muscle gene in the nematode C. elegans. Antibodies specific to CPNA-1, as well as a YFP translational fusion, are localized to integrin attachment sites (M-lines and dense bodies) in the body-wall muscle of C. elegans. CPNA-1 contains an N-terminal predicted transmembrane domain and a C-terminal copine domain, and binds to the M-line/dense body protein PAT-6 (actopaxin) and the M-line proteins UNC-89 (obscurin), LIM-9 (FHL), SCPL-1 (SCP) and UNC-96. Proper CPNA-1 localization is dependent upon PAT-6 in embryonic and adult muscle. Nematodes lacking cpna-1 arrest elongation at the twofold stage of embryogenesis, and display disruption of the myofilament lattice. The thick filament component myosin heavy chain MYO-3, and the M-line component UNC-89, are initially localized properly in cpna-1 null embryos. However, in these embryos, when contraction begins, MYO-3 and UNC-89 become mislocalized into large foci and animals die. We propose that CPNA-1 acts as a linker between an integrin associated protein, PAT-6, and membrane-distal components of integrin adhesion complexes in the muscle of C. elegans.
    Molecular biology of the cell 01/2013; 24(5). DOI:10.1091/mbc.E12-06-0478 · 4.47 Impact Factor
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    ABSTRACT: Tubulobulbar complexes are actin-related endocytic structures that form at sites of intercellular attachment in the seminiferous epithelium and are proposed to internalize intact junctions. In this study, we test the prediction that altering the structure/function of tubulobulbar complexes results in failure to release mature spermatids from Sertoli cells. We used an in vivo knockdown strategy to target cortactin, a component of tubulobulbar complexes, in Sprague Dawley rats. In each animal, one testis was surgically injected with cortactin siRNA reagents and the other testis was injected with non-targeting siRNA. After three days, experimental and control testes were processed for immunoblotting, electron microscopy or immunofluorescence microscopy. In testis sections immunostained for cortactin or labeled for filamentous actin, fluorescence microscopy revealed that tubulobulbar complexes were shorter in siRNA-treated testes relative to controls. Significantly, in the knockdown testes, spermiation was delayed in some tubules and had failed in others. When evaluated by electron microscopy, adhesion complexes (ectoplasmic specializations) remained associated with mature spermatids that failed to be released from Sertoli cells. Immunoblots both of whole testis lysates and of isolated seminiferous epithelial lysates confirmed that cortactin expression was knocked-down in experimental testes and in the seminiferous epithelium respectively, relative to controls. Moreover, in testes injected with siRNA reagents with a dye modification on one of the four targeting siRNA sequences, dye clusters were detected at the base of the epithelium confirming that the reagents entered Sertoli cells. Our results are consistent with the hypothesis that tubulobulbar complexes internalize intercellular junctions and that they are a significant component of the sperm release mechanism.
    Biology Open 11/2012; 1(11):1069-77. DOI:10.1242/bio.20122519 · 2.42 Impact Factor
  • Jaehyuk Choi · A Wayne Vogl · James W Kronstad
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    ABSTRACT: Cyclic AMP-dependent protein kinase A (PKA) regulates elaboration of the virulence factors melanin and polysaccharide capsule in Cryptococcus neoformans. A mutation in PKA1 encoding the catalytic subunit is known to reduce virulence in mice while a defect in PKR1 encoding the regulatory subunit enhances disease. Here, we constructed strains with galactose-inducible and glucose-repressible versions of PKA1 and PKR1 by inserting the GAL7 promoter upstream of the genes. As expected, no capsule was found in dextrose-containing media for the P(GAL7):PKA1 strain, whereas a large capsule was formed on cells grown in galactose. Along with capsule thickness, high PKA activity also influenced cell size, ploidy and vacuole enlargement, as observed in previous reports of giant/titan cell formation. We employed the regulated strains to test the hypothesis that PKA influences secretion and found that elevated PKA expression positively regulates extracellular protease activity and negatively regulates urease secretion. Furthermore, proper PKA regulation and activity were required for wild-type levels of melanization and laccase activity, as well as correct localization of the enzyme. The latter phenotype is consistent with the discovery that PKA regulates the organization of intracellular membrane compartments. Overall, these results indicate that PKA influences secretion pathways directly related to virulence factor elaboration.
    Molecular Microbiology 06/2012; 85(4):700-15. DOI:10.1111/j.1365-2958.2012.08134.x · 4.42 Impact Factor

Publication Stats

3k Citations
337.03 Total Impact Points


  • 1985–2015
    • University of British Columbia - Vancouver
      • • Department of Cellular and Physiological Sciences
      • • Faculty of Medicine
      • • Department of Zoology
      Vancouver, British Columbia, Canada
  • 1987–1988
    • Southern Illinois University Carbondale
      • Department of Physiology
      Carbondale, IL, United States
  • 1983
    • Harvard Medical School
      Boston, Massachusetts, United States