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Immunoglobulin Superfamily Protein Dscam Exhibited Molecular Diversity by Alternative Splicing in Hemocytes of Crustacean, Eriocheir Sinensis

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Immunoglobulin Superfamily Protein Dscam Exhibited Molecular Diversity by Alternative Splicing in Hemocytes of Crustacean, Eriocheir Sinensis See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/249647279 Immunoglobulin superfamily protein Dscam exhibited molecular diversity by alternative splicing in hemocytes of crustacean, Eriocheir sinensis ARTICLE in FISH &AMP SHELLFISH IMMUNOLOGY · JULY 2013 Impact Factor: 2.67 · DOI: 10.1016/j.fsi.2013.06.029 · Source: PubMed CITATIONS READS 7 129 9 AUTHORS, INCLUDING: Xing-Kun Jin Wei-Wei Li East China Normal University East China Normal University 20 PUBLICATIONS 117 CITATIONS 28 PUBLICATIONS 241 CITATIONS SEE PROFILE SEE PROFILE Minhao Wu Qun Wang East China Normal University East China Normal University 10 PUBLICATIONS 59 CITATIONS 72 PUBLICATIONS 682 CITATIONS SEE PROFILE SEE PROFILE Available from: Qun Wang Retrieved on: 11 October 2015 Fish & Shellfish Immunology 35 (2013) 900e909 Contents lists available at SciVerse ScienceDirect Fish & Shellfish Immunology journal homepage: www.elsevier.com/locate/fsi Immunoglobulin superfamily protein Dscam exhibited molecular diversity by alternative splicing in hemocytes of crustacean, Eriocheir sinensis Xing-Kun Jin 1, Wei-Wei Li 1, Min-Hao Wu, Xiao-Nv Guo, Shuang Li, Ai-Qing Yu, You-Ting Zhu, Lin He, Qun Wang* Department of Biology, School of Life Science, East China Normal University, No. 3663 North Zhong-Shan Road, Shanghai, China article info abstract Article history: Be absent of adaptive immunity which have both specificity and memory, invertebrates seem to have Received 16 April 2013 evolved alternative adaptive immune strategies to resist various intruding pathogens. Whereas verte- Received in revised form brates could generate a wide range of immunological receptors with somatic rearrangement, in- 20 June 2013 vertebrates possibly depend on alternative splicing of pattern-recognition receptors (PRRs). Recently, it Accepted 27 June 2013 has been suggested that a member of the immunoglobulin superfamily (IgSF), Down syndrome cell Available online 13 July 2013 adhesion molecule (Dscam), plays a crucial role in the alternative adaptive immune system of in- vertebrates. At present, we successfully isolated and characterized the first crab Dscam from Eriocheir Keywords: Alternative adaptive immune sinensis. EsDscam has typical domain architecture compared with other Dscam orthologs, including one fi Chinese mitten crab signal-peptide, 10 immunoglobulin (Ig) domains, 6 bronectin type III domains (FNIII), one trans- Down syndrome cell adhesion molecule membrane domain (TM) and one cytoplasmic tail. We had detected four hypervariable regions of (Dscam) EsDscam in the N-terminal halves of Ig2 (25) and Ig3 domain (30), the complete Ig7 (18) and also the Immunoglobulin domain transmembrane domain (2), potentially generate 27,000 unique isoforms at least. Transcription of Pathogen associated molecular patterns EsDscam were both a) detected in all tissues, especially in immune system, digestive system and nerve (PAMPs) system; b) significantly induced in hemocytes post lipopolysaccharides (LPS), peptidoglycans (PG) and b-1, 3-glucans (Glu) injection. Importantly, we had detected membrane-bound and secreted Dscam isoforms in E. sinensis, and showed that secreted isoforms were extensively transcribed post different PAMPs challenge respectively. Results from immuno-localization assay revealed that EsDscam evenly distributed in the cell surface of hemocytes. These findings indicated that EsDscam is a hypervariable PRR in the innate immune system of the E. sinensis. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction had successfully survived under the long time evolution pressure from various kinds of pathogens, hence they must have sufficient With the ongoing pressure for survival, animals evolved potential to diversify their immune strategies comparable with refinement of intricate immune systems to distinguish and elimi- those confronting jawed vertebrates [3]. In the last few years, a nate foreign “non-self” to maintain self-owned health, which plenty of studies had indeed observed the phenomenon that some consist of innate immune and adaptive immune [1]. Up to now, only degree of immune specificity existed in invertebrates, such as flea higher vertebrates were found to both have innate and adaptive (Daphnia magna), bumblebee (Bombus terrestris), fruit fly immunity which achieved through the vast diversity of somatically (Drosophila melanogaster), beetle (Tribolium castaneum) and shrimp rearranged immunological receptors such as antibodies [2]. (Litopenaeus vannamei) [4e8]. Invertebrates seem to have emerged Invertebrates rely solely on innate immunity as their major different ways to enable challenge-specific protection serving the mechanism to fight against pathogens intruding without any “true” same functionality as vertebrate adaptive immunity to some extent lymphocytes and functional antibody. Nevertheless, invertebrate [9]. The analogous recognition function of these remarkably different immune systems involved innovative genetic modifica- tion of innate-immune-system components, such as Immuno- * þ þ globulin Superfamily (IgSF) proteins [10]. The IgSF molecules Corresponding author. Tel.: 86 (0) 21 54345224; fax: 86 (0) 21 62233754. fl E-mail addresses: [email protected], [email protected] (Q. Wang). appear either at the cell surface or in body uid, bind diverse 1 These two authors contribute equally to this work. ligands, and contribute to a variety of cellular activities, including 1050-4648/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fsi.2013.06.029 X.-K. Jin et al. / Fish & Shellfish Immunology 35 (2013) 900e909 901 adhesion and immune responses in both vertebrates (also known crabs were injected into the arthrodial membrane of the last pair of as antibodies) and invertebrates [11]. In gastropod, fresh snail IgSF walking legs with approximately 100 ml of lipopolysaccharides (LPS molecules, the Ig domain-containing, fibrinogen-related proteins from E. coli, SigmaeAldrich), 100 ml of peptidoglycan (PG from (FREPs), were found to been capable of generating diverse mole- S. aureus, SigmaeAldrich) and 100 ml of zymosan (Glu from cules involved in internal defense [12]. In arthropods, more and S. cerevisiae, SigmaeAldrich) resuspended (500 mg/mL) in ESS more Dscam orthologs were found to have exons alternative (Eriocheir sinensis saline, 0.2 M NaCl, 5.4 mM KCl, 10.0 mM CaCl2, splicing features [13e19], and even acted as the central immune 2.6 mM MgCl2, 2.0 mM NaHCO3; pH 7.4) [18,23,24]; while one surveillance factors with extensive molecular diversity in inverte- control group with 100 ml ESS (pH 7.4). More than five crabs were brate innate immune system [13,14,16,18,19]. randomly selected at each time interval of 0 (as blank control), 2, 6, DSCAM, one of the largest IgSF members (220 kDa) discovered 12 and 24 h post each kind of PAMPs injection. Hemocytes were containing 10 Ig domains and 6 fibronectin type III (FN) domains, harvested according to methods above, and were stored at À80 C, which was first identified in the human chromosome 21q22 asso- after the addition of 1 mL Trizol reagent (Invitrogen, CA, USA) for ciated with Down Syndrome [20]. Invertebrate Dscam was initially subsequent RNA extraction. discovered as an axon guidance receptor in insect nerve system, serving the same function as higher vertebrate [21]. Yet, in the 2.2. Total RNA extraction and first-strand cDNA synthesis N-terminal halves of the Ig2 and Ig3, the full Ig7 and trans- membrane domain, highly variable exons generated by alternative Total RNA was extracted from E. sinensis tissues sampled from Ò splicing were detected, may amazingly yield more than 38,000 Section 2.1 using Trizol reagent (RNA Extraction Kit, Invitrogen, unique isoforms, which were never been found in vertebrate CA, USA) according to the manufacturer’s protocol. The total RNA DSCAM [21]. Subsequently, in fat body cells and hemocytes, which concentration and quality were estimated using spectrophotom- both were major tissues of the insect immune system, Dscam was etry at an absorbance at 260 nm and agarose-gel electrophoresis found extensively expressed. Moreover, the immune function of respectively. Dscam was unveiled for its participation in bacteria recognition and Total RNA (5 mg) isolated from testis and hemocytes was reverse phagocytosis [13,14]. transcribed using the SMARTerÔ RACE cDNA Amplification kit In the present study, we investigate how this novel invertebrate (Clonetech, USA) for full-length cDNA cloning. For Quantitative RT- pattern recognition receptor (PRR) might be involved in the innate PCR expression analysis, total RNA (4 mg) was reverse transcribed immune response in crab. Base on the initial sequences from our using the PrimeScriptÔ Real-time PCR Kit (TaKaRa, Japan). previously constructed Eriocheir sinensis transcriptome profiles of testis [22], and hemocytes (unpublished), we firstly cloned and 2.3. Cloning of full length EsDscam cDNA characterized the EsDscam full-length cDNA sequence, not only identified its domain architecture but also compared its phyloge- Eriocheir sinensis Dscam partial cDNA sequence was extended netic similarity among animal orthologs. Detected the hypervari- using 50 and 30 RACE (SMARTerÔ RACE cDNA Amplification kit, able regions in the N-terminal halves of the Ig2 and the Ig3 Clontech), and designed gene-specific primers (Table S1, Fig. S1) domains, the entire Ig7 domain, and the transmembrane domain, based on the original transcriptome sequences from testis [22] and by which altogether not
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