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Horm Metab Res 2015; 47(02): 114-118
DOI: 10.1055/s-0034-1385903
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Phosducin Regulates Secretory Activity in TT Line of Thyroid Parafollicular C Cells

U. Piotrowska
1   Department of Biochemistry and Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland
,
G. Adler
1   Department of Biochemistry and Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland
,
I. Kozicki
2   Department of General Surgery, Medical Center of Postgraduate Education, Warsaw, Poland
› Institutsangaben
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Publikationsverlauf

received 18. Februar 2014

accepted 09. Juli 2014

Publikationsdatum:
25. August 2014 (online)

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Abstract

The endocrine activity of the thyroid gland is accomplished by its follicular and parafollicular cells. In these cells, numerous G proteins-dependent pathways are active and potentially could be regulated by a 33-kDa cytoplasmic protein phosducin, which interacts with the Gβ subunit and may compete with Gα or Gβγ dimer effectors. Significant expression of phosducin has been shown in the retina, pineal gland, and some neurons. Here, we studied postoperative thyroid tissue samples collected from patients with nodular goiter and 2 thyroid-derived cell lines for the presence of phosducin. Using reverse transcription PCR with product sequencing and highly sensitive immunodetection we identified phosducin mRNA and protein in the thyroid gland and parafollicular C TT cells, but not in the follicular Nthy-ori 3-1 cell line. We also observed that siRNA-mediated silencing of phosducin gene expression decreased Ca2+-stimulated secretion of calcitonin and serotonin by TT cells.

Key words

calcium - calcitonin - serotonin - medullary thyroid carcinoma TT cells - phosducin - thyroid
 

  • References

  • 1 Schulz R. The pharmacology of phosducin. Pharmacol Res 2001; 43: 1-10
    CrossrefPubMedGoogle Scholar
  • 2 Beetz N, Hein L. The physiological roles of phosducin: from retinal function to stress dependent hypertension. Cell Mol Life Sci 2011; 68: 599-612
    CrossrefPubMedGoogle Scholar
  • 3 Willardson BM, Howlett AC. Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding. Cell Signal 2007; 19: 2417-2427
    CrossrefPubMedGoogle Scholar
  • 4 Krispel CM, Sokolov M, Chen YM, Song H, Herrmann R, Arshavsky VY, Burns ME. Phosducin regulates the expression of transducin βγ subunits in rod photoreceptors and does not contribute to phototransduction adaptation. J Gen Physiol 2007; 130: 303-312
    CrossrefPubMedGoogle Scholar
  • 5 Herrmann R, Lobanova ES, Hammond T, Kessler C, Burns ME, Frishman LJ, Arshavsky VY. Phosducin Regulates Transmission at the Photoreceptor-to-ON-Bipolar Cell Synapse. J. Neurosci 2010; 30: 3239-3253
    CrossrefPubMedGoogle Scholar
  • 6 Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM. Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly. EMBO J 2005; 24: 1965-1975
    CrossrefPubMedGoogle Scholar
  • 7 Danner S, Lohse MJ. Phosducin is a ubiquitous G-protein regulator. Proc Natl Acad Sci 1996; 93: 10145-10150
    CrossrefPubMedGoogle Scholar
  • 8 Beetz N, Harrison MD, Brede M, Zong X, Urbanski MJ, Sietmann A, Kaufling J, Lorkowski S, Barrot M, Seeliger MW, Vieira-Coelho MA, Hamet P, Gaudet D, Seda O, Tremblay J, Kotchen TA, Kaldunski M, Nusing R, Szabo B, Jacob HJ, Cowley Jr AW, Biel M, Stoll M, Lohse MJ, Broeckel U, Hein L. Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice. J Clin Invest 2009; 119: 3597-3612
    PubMedGoogle Scholar
  • 9 Di Comite G, Grazia Sabbadini M, Corti A, Rovere-Querini P, Manfredi AA. Conversation galante: how the immune and the neuroendocrine systems talk to each other. Autoimmun Rev 2007; 7: 23-29
    CrossrefPubMedGoogle Scholar
  • 10 Toni R. The neuroendocrine system: Organization and homeostatic role. J Endocrinol Invest 2004; 27 (Suppl to No. 6) 35-47
    PubMedGoogle Scholar
  • 11 Tamir H, Liu KP, Payette RF, Hsiung SC, Adlersberg M, Nunez EA, Gershon MD. Human medullary thyroid carcinoma: characterization of the serotonergic and neuronal properties of a neurectodermally derived cell line. J Neurosci 1989; 9: 1199-1212
    PubMedGoogle Scholar
  • 12 Barasch JM, Tamir H, Nunez EA, Gershon MD. Serotonin-storing secretory granules from thyroid parafollicular cells. J Neurosci 1987; 7: 4017-4033
    PubMedGoogle Scholar
  • 13 Biagi BA, Mlinar B, Enyeart JJ. Membrane currents in a calcitonin-secreting human C cell line. Am J Physiol Cell Physiol 1992; 263: C986-C994
    PubMedGoogle Scholar
  • 14 Mehrke G, Zong XG, Flockerzi V, Hofmann F. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L- type Ca++ channels. J Pharmacol Exp Ther 1994; 271: 1483-1488
    PubMedGoogle Scholar
  • 15 Raue F, Scherübl H. Extracellular calcium sensitivity and voltage-dependent calcium channels in C cells. Endocr Rev 1995; 16: 752-764
    PubMedGoogle Scholar
  • 16 Zabel M, Grzeszkowiak J. Characterisation of thyroid medullary carcinoma TT cell line. Histol Histopathol 1997; 12: 283-289
    PubMedGoogle Scholar
  • 17 Piotrowska U, Adler G. Phosducin and monomeric beta-actin have common epitope recognized by anti-phosducin antibodies. Immunol Lett 2010; 134: 62-68
    CrossrefPubMedGoogle Scholar
  • 18 Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F. Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 1996; 137: 3842-3848
    CrossrefPubMedGoogle Scholar
  • 19 McGehee DS, Aldersberg M, Liu KP, Hsuing S, Heath MJ, Tamir H. Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells. J Physiol 1997; 502: 31-44
    CrossrefPubMedGoogle Scholar
  • 20 Tamir H, Liu KP, Adlersberg M, Hsiung SC, Gershon MD. Acidification of Serotonin-containing Secretory Vesicles Induced by a Plasma Membrane Calcium Receptor. J Biol Chem 1996; 271: 6441-6450
    CrossrefPubMedGoogle Scholar
  • 21 Tamir H, Piscopo I, Liu KP, Hsiung SC, Adlersberg M, Nicolaides M, Alawquati Q, Nunez EA, Gershon D. Secretogogue-induced gating of chloride channels in the secretory vesicles of parafollicular cells. Endocrinology 1994; 135: 2045-2057
    PubMedGoogle Scholar
  • 22 Blackmer T, Larsen EC, Bartleson C, Kowalchyk JA, Yoon EJ, Preininger AM, Alford S, Hamm HE, Martin TF. G protein βγ directly regulates SNARE protein fusion machinery for secretory granule exocytosis. Nat Neurosci 2005; 8: 421-425
    PubMedGoogle Scholar
  • 23 Gensse M, Vitale N, Chasserot-Golaz S, Bader MF. Regulation of exocytosis in chromaffin cells by phosducin-like protein, a protein interacting with G protein βγ subunits. FEBS Lett 2000; 480: 184-188
    CrossrefPubMedGoogle Scholar
  • 24 Long JH, Arshavsky VY, Burns ME. Absence of Synaptic Regulation by Phosducin in Retinal Slices. Plos One 2013; 8: 1-8
    PubMedGoogle Scholar
  • 25 Thomsen ARB, Worm J, Jacobsen SE, Stahlhut M, Latta M, Bräuner-Osborne H. Strontium Is a Biased Agonist of the Calcium-Sensing Receptor in Rat Medullary Thyroid Carcinoma 6-23 Cells. J Pharmacol Exp Ther 2012; 343: 638-649
    CrossrefPubMedGoogle Scholar
  • 26 Lu CC, Tsai SC. The cyclic AMP-dependent protein kinase A pathway is involved in progesterone effects on calcitonin secretion from TT cells. Life Sci 2007; 81: 1411-1420
    CrossrefPubMedGoogle Scholar
  • 27 Lu CC, Tsai SC. Involvement of the cyclic-AMP-dependent protein kinase A pathway in thyroxine effects on calcitonin secretion from TT cells. Horm Metab Res 2011; 43: 31-36
    Artikel in Thieme ConnectPubMedGoogle Scholar