Spaetzle

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Spaetzle
Precursor 326 amino acids , 37,447 Da
Identifier
External IDs
Orthologue (fruit fly)
Entrez 43256
UniProt P48607
Refseq (mRNA) NM_001144644.2
Refseq (protein) NP_001138116.1
PubMed search 43256

Spaetzle (also Spätzle ) is a protein from the fruit fly Drosophila melanogaster , which is involved in embryonic development and in activating the innate immune response . The name was the Nobel laureate Christiane Nüsslein-Volhard and colleagues in accordance with the noodles of -like shape larvae of melanogaster D. embossed, when the gene of Spaetzle homozygous mutated and the protein encoded thereby is no longer formed functional (as well as Gene of the protein noodle ).

properties

Comparison of the Toll signaling pathway in mammals, shrimp, and fruit flies

Spaetzle binds as a homodimer to the toll receptor (a dimeric receptor ) in fruit flies. By alternative splicing of several be isoforms formed by Spaetzle. Spaetzle is formed as a preprotein and after activation of the serine protease Spaetzle-processing enzymes it is broken down into the active form. After splitting off the signal sequence , Spaetzle (consisting of amino acids 26–326) results and after a further split the C -terminal protein fragment Spaetzle C106 (amino acids 221–326). Spaetzle has disulfide bridges and is glycosylated .

Embryonic development

In the embryonic development of the fruit flies, Spaetzle is involved in the formation of the dorsoventral axis. As a result of the activation of the Toll receptor in the cell membrane of the embryonic cells, the transcription factor dorsal is formed via signal transduction , with a concentration gradient from ventral to dorsal in the cell nuclei of the embryonic cells in the blastoderm stage . The Dorsal protein determines the spatially specific gene expression of many genes in the zygote , which are known as the Dorsal gene regulatory network .

Innate immune system

The Spaetzle processing enzyme is activated by proteolysis after various components of D. melanogaster pathogens ( gram-positive bacteria , yeasts and other fungi ) have bound to proteases . After activation of the Toll receptor by binding a Spaetzle dimer, MyD88 is first bound intracellularly to the Toll receptor and then an unknown adapter protein , tube and the protein kinase Pelle . In the further course, Cactus is proteolytically degraded and the transcription factor Dorsal-related Immunity Factor (DIF), which was previously bound to Cactus, is released, which is transported into the cell nucleus and as a dimer initiates the gene expression of antimicrobial peptides , including the antifungal peptide drosomycin .

Individual evidence

  1. ↑ D. Stein, C. Nüsslein-Volhard: Multiple extracellular activities in Drosophila egg perivitelline fluid are required for establishment of embryonic dorsal-ventral polarity. In: Cell . Volume 68, Number 3, February 1992, pp. 429-440, PMID 1739964 .
  2. ↑ a b Christiane Nüsslein-Volhard in Biology - Student Lexicon - Learning Helpers. In: lernhelfer.de. 2010, accessed December 18, 2018 .
  3. ↑ E. Seifert, F. Müller-Holtkamp, ​​D. Marcey, H. Jäckle: Injection of wild-type cytoplasm and poly (A) RNA provokes phenotype rescue in spätzle mutant Drosophila embryos. In: Roux's archives of developmental biology  : the official organ of the EDBO. Volume 196, Number 2, February 1987, pp. 78-82, doi : 10.1007 / BF00402028 , PMID 28305461 .
  4. ↑ TO Weber, S. Tauszig-Delamasure, JA Hoffmann, E. Lelièvre, H. Gascan, KP Ray, MA Morse, JL Imler, NJ Gay: Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling. In: Nature Immunology . Volume 4, Number 8, August 2003, pp. 794-800, doi : 10.1038 / ni955 , PMID 12872120 .
  5. ↑ a b Y. DeLotto, C. Smith, R. DeLotto: multiple isoforms of the Drosophila protein noodles are encoded by alternatively spliced mRNAs in the maternal precellular blastoderm embryo. In: Molecular & general genetics  : MGG. Volume 264, Number 5, January 2001, pp. 643-652, PMID 11212919 .
  6. ↑ a b spz - Protein spaetzle precursor - Drosophila melanogaster (Fruit fly) - spz gene & protein. In: uniprot.org. November 7, 2018, accessed December 18, 2018 .
  7. ↑ D. Morisato, KV Anderson: The spätzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. In: Cell . Volume 76, Number 4, February 1994, pp. 677-688, doi : 10.1016 / 0092-8674 (94) 90507-X , PMID 8124709 .
  8. ↑ a b D. S. Stein, LM Stevens: Maternal control of the Drosophila dorsal-ventral body axis. In: Wiley interdisciplinary reviews. Developmental biology. Volume 3, number 5, 2014 Sep-Oct, pp. 301-330, doi : 10.1002 / wdev.138 , PMID 25124754 , PMC 4724419 (free full text).
  9. ↑ S. Kurata: Peptidoglycan recognition proteins in Drosophila immunity. In: Developmental & Comparative Immunology . Volume 42, number 1, January 2014, pp. 36-41, doi : 10.1016 / j.dci.2013.06.006 , PMID 23796791 , PMC 3808481 (free full text).
  10. ↑ S. Valanne, JH Wang, M. Rämet: The Drosophila Toll signaling pathway. In: Journal of Immunology . Volume 186, Number 2, January 2011, pp. 649-656, doi : 10.4049 / jimmunol.1002302 , PMID 21209287 .
  11. ↑ JJ Sun, S. Xu, ZH He, XZ Shi, XF Zhao, JX Wang: Activation of Toll Pathway Is Different between Kuruma Shrimp and. In: Frontiers in Immunology . Volume 8, 2017, p. 1151, doi : 10.3389 / fimmu.2017.01151 , PMID 28979261 , PMC 5611483 (free full text).
  12. ↑ B. Lemaitre, E. Nicolas, L. Michaut, JM Reichhart, JA Hoffmann: The dorsoventral regulatory gene cassette spätzle / Toll / cactus controls the potent antifungal response in Drosophila adults. In: Cell . Volume 86, Number 6, September 1996, pp. 973-983, doi : 10.1016 / S0092-8674 (00) 80172-5 , PMID 8808632 .