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Full-Text Articles in Cell Biology

Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk May 2015

Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk

Sean P. Ryder

Although the decision between stem cell self-renewal and differentiation has been linked to cell-cycle modifications, our understanding of cell-cycle regulation in stem cells is very limited. Here, we report that FBF/Pumilio, a conserved RNA-binding protein, promotes self-renewal of germline stem cells by repressing CKI-2(Cip/Kip), a Cyclin E/Cdk2 inhibitor. We have previously shown that repression of CYE-1 (Cyclin E) by another RNA-binding protein, GLD-1/Quaking, promotes germ cell differentiation. Together, these findings suggest that a post-transcriptional regulatory circuit involving FBF and GLD-1 controls the self-renewal versus differentiation decision in the germline by promoting high CYE-1/CDK-2 activity ...


A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano Apr 2015

A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano

Nils Henninger

BACKGROUND AND AIMS: Glomerular diseases are the third leading cause of kidney failure worldwide, behind only diabetes and hypertension. The molecular mechanisms underlying the cause of glomerular diseases are still largely unknown. The identification and characterization of new molecules associated with glomerular function should provide new insights into understanding the diverse group of glomerular diseases. The Chd2 protein belongs to a family of enzymes involved in ATP-dependent chromatin remodeling, suggesting that it likely functions as an epigenetic regulator of gene expression via the modification of chromatin structure. METHODS: In this study, we present a detailed histomorphologic characterization of mice containing ...


Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee Sep 2014

Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both ...


P19ink4d And P18ink4c Cyclin-Dependent Kinase Inhibitors In The Male Reproductive Axis, Gregory Buchold, Patricia Magyar, Ramamani Arumugam, Mary Lee, Deborah O'Brien Sep 2014

P19ink4d And P18ink4c Cyclin-Dependent Kinase Inhibitors In The Male Reproductive Axis, Gregory Buchold, Patricia Magyar, Ramamani Arumugam, Mary Lee, Deborah O'Brien

Mary M. Lee

The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are ...


Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe Sep 2014

Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe

Mary M. Lee

We have isolated a candidate Mullerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II ...


Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck Sep 2014

Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck

Mary M. Lee

Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is ...


The Influence Of Endocrine Disruptors On Pubertal Timing, Elka Jacobson-Dickman, Mary Lee Sep 2014

The Influence Of Endocrine Disruptors On Pubertal Timing, Elka Jacobson-Dickman, Mary Lee

Mary M. Lee

PURPOSE OF REVIEW: Overview of the effects of endocrine disruptors on pubertal timing. RECENT FINDINGS: Epidemiologic studies in humans support animal data demonstrating that exposures to endocrine-disrupting compounds have pronounced effects on pubertal timing and that the timing of endocrine-disrupting compound exposure and the specific agent causes different outcomes. Recent studies confirm subtle effects of lead, dioxins, and phytoestrogens on delaying onset of puberty and demonstrate an association of phthalates and polychlorinated biphenyls with earlier breast development and menarche, respectively. These studies, however, are complicated by mixed exposures of compounds which individually may have opposing actions on the reproductive axis ...


Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee Sep 2014

Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered ...


Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe Sep 2014

Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian ...


Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe Sep 2014

Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe

Mary M. Lee

Mullerian Inhibiting Substance (MIS) production in rat testes from the late fetal to the adult period and its modulation by gonadotropins in neonatal testes were studied using immunohistochemistry, northern analysis, and a graded organ culture bioassay for MIS. The intense immunohistochemical staining for MIS seen in fetal and newborn testes began to decrease gradually after the third postnatal day, then decreased dramatically on the fifth postnatal day. MIS immunohistochemical activity was then present at a low level until about the 20th postnatal day, after which it was barely detectable. The testes from rats treated with FSH at birth showed a ...


Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee Sep 2014

Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ...


Androgen Profiles During Pubertal Leydig Cell Development In Mice, Xiufeng Wu, Ramamani Arumugam, Ningning Zhang, Mary Lee Sep 2014

Androgen Profiles During Pubertal Leydig Cell Development In Mice, Xiufeng Wu, Ramamani Arumugam, Ningning Zhang, Mary Lee

Mary M. Lee

Postnatal Leydig cell (LC) development in mice has been assumed empirically to resemble that of rats, which have characteristic hormonal profiles at well-defined maturational stages. To characterize the changes in LC function and gene expression in mice, we examined reproductive hormone expression from birth to 180 days, and quantified in vivo and in vitro production of androgens during sexual maturation. Although the overall plasma androgen and LH profiles from birth through puberty were comparable to that of rats, the timing of developmental changes in androgen production and steroidogenic capacity of isolated LCs differed. In mice, onset of androgen biosynthetic capacity ...


Developmental Changes In Mullerian Inhibiting Substance In The Cynomolgus Monkey, Macaca Fascicularis, Mary Lee, M. Gustafson, Etsuji Ukiyama, Patricia Donahoe, David Maclaughlin, Michael Wexler, Hugh Keeping Sep 2014

Developmental Changes In Mullerian Inhibiting Substance In The Cynomolgus Monkey, Macaca Fascicularis, Mary Lee, M. Gustafson, Etsuji Ukiyama, Patricia Donahoe, David Maclaughlin, Michael Wexler, Hugh Keeping

Mary M. Lee

Mullerian inhibiting substance (MIS) is a glycoprotein hormone produced in Sertoli cells of the fetal and postnatal testis, and granulosa cells of the pubertal ovary. We examined MIS expression in a nonhuman primate, the cynomolgus macaque monkey (Macaca fascicularis), to define an animal model for studying MIS gene regulation. Changes in testicular MIS mRNA with age were assessed by in situ hybridization of prepubertal to adult testes, Northern analysis of pubertal and adult specimens, and determination of serum MIS concentrations from infancy to adulthood. We found that MIS expression was highest in the youngest animals and decreased progressively with increasing ...


Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy Sep 2014

Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy

Mary M. Lee

Mullerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Mullerian duct involution during male sexual differentiation. Mice with null mutations of the MIS ligand or receptor develop Leydig cell hyperplasia and neoplasia in addition to retained Mullerian ducts, whereas MIS-overexpressing transgenic mice have decreased testosterone concentrations and Leydig cell numbers. We hypothesized that MIS directly modulates Leydig cell proliferation and differentiated function in the maturing testis. Therefore, highly purified rat Leydig and Sertoli cells were isolated to examine cell-specific expression, binding, and function of the MIS type II receptor. These studies revealed that this receptor is ...


A Single Base Pair Mutation Encoding A Premature Stop Codon In The Mis Type Ii Receptor Is Responsible For Canine Persistent Mullerian Duct Syndrome, Wenfang Wu, Shengqin Wan, Pujar Shashikant, Mark Haskins, Donald Schlafer, Mary Lee, Vicki Meyers-Wallen Sep 2014

A Single Base Pair Mutation Encoding A Premature Stop Codon In The Mis Type Ii Receptor Is Responsible For Canine Persistent Mullerian Duct Syndrome, Wenfang Wu, Shengqin Wan, Pujar Shashikant, Mark Haskins, Donald Schlafer, Mary Lee, Vicki Meyers-Wallen

Mary M. Lee

Mullerian inhibiting substance (MIS), a secreted glycoprotein in the transforming growth factor-beta family of growth factors, mediates regression of the Mullerian ducts during embryonic sex differentiation in males. In persistent Mullerian duct syndrome (PMDS), rather than undergoing involution, the Mullerian ducts persist in males, giving rise to the uterus, fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited ...


Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate Sep 2014

Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate

Mary M. Lee

Mullerian inhibiting substance (MIS), a testicular glycoprotein also known as anti-Mullerian hormone, plays a key role in male sexual development by causing regression of the Mullerian duct, the anlagen of the uterus, the Fallopian tubes, and part of the vagina. MIS is also expressed in the postnatal ovary, but its precise function is still not known. We report here the complete nucleotide sequence of the rat MIS gene. Rat MIS is encoded in five exons and is synthesized as a precursor of 553 amino acids, containing a 24-amino-acid leader. Based on homology with human MIS, we predict that the rat ...


Effect Of E. Coli Endotoxin On Mammalian Cell Growth And Recombinant Protein Production, J. Epstein, Mary Lee, C. Kelly, Patricia Donahoe Sep 2014

Effect Of E. Coli Endotoxin On Mammalian Cell Growth And Recombinant Protein Production, J. Epstein, Mary Lee, C. Kelly, Patricia Donahoe

Mary M. Lee

No abstract provided.


Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe Sep 2014

Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe

Mary M. Lee

In males, Mullerian inhibiting substance (MIS) mRNA was first detected on the medial aspect of the urogenital ridge early on the morning of day 13 of gestation before testicular differentiation was evident, and localized to the more obvious Sertoli cells later on embryonic day 13. MIS transcripts remained at maximal levels between 14.5 and 17.5 days gestation, while the Mullerian duct involutes, and remained high until birth. MIS gene expression decreased progressively after birth and, as germ cell meiosis increased, became barely detectable in the Sertoli cells of the seminiferous tubules. In female rats, MIS mRNA was first ...


Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas Sep 2013

Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas

Stanley D Dunn

Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit ...


Novel Interactors And A Role For Supervillin In Early Cytokinesis, Tara Smith, Zhiyou Fang, Elizabeth Luna Mar 2011

Novel Interactors And A Role For Supervillin In Early Cytokinesis, Tara Smith, Zhiyou Fang, Elizabeth Luna

Elizabeth J. Luna

Supervillin, the largest member of the villin/gelsolin/flightless family, is a peripheral membrane protein that regulates each step of cell motility, including cell spreading. Most known interactors bind within its amino (N)-terminus. We show here that the supervillin carboxy (C)-terminus can be modeled as supervillin-specific loops extending from gelsolin-like repeats plus a villin-like headpiece. We have identified 27 new candidate interactors from yeast two-hybrid screens. The interacting sequences from 12 of these proteins (BUB1, EPLIN/LIMA1, FLNA, HAX1, KIF14, KIFC3, MIF4GD/SLIP1, ODF2/Cenexin, RHAMM, STARD9/KIF16A, Tks5/SH3PXD2A, TNFAIP1) co-localize with and mis-localize EGFP-supervillin in mammalian ...


The Membrane-Associated Protein, Supervillin, Accelerates F-Actin-Dependent Rapid Integrin Recycling And Cell Motility, Zhiyou Fang, Norio Takizawa, Korey Wilson, Tara Smith, Anna Delprato, Michael Davidson, David Lambright, Elizabeth Luna Mar 2011

The Membrane-Associated Protein, Supervillin, Accelerates F-Actin-Dependent Rapid Integrin Recycling And Cell Motility, Zhiyou Fang, Norio Takizawa, Korey Wilson, Tara Smith, Anna Delprato, Michael Davidson, David Lambright, Elizabeth Luna

Elizabeth J. Luna

In migrating cells, the cytoskeleton coordinates signal transduction and redistribution of transmembrane proteins, including integrins and growth factor receptors. Supervillin is an F-actin- and myosin II-binding protein that tightly associates with signaling proteins in cholesterol-rich, 'lipid raft' membrane microdomains. We show here that supervillin also can localize with markers for early and sorting endosomes (EE/SE) and with overexpressed components of the Arf6 recycling pathway in the cell periphery. Supervillin tagged with the photoswitchable fluorescent protein, tdEos, moves both into and away from dynamic structures resembling podosomes at the basal cell surface. Rapid integrin recycling from EE/SE is inhibited ...