Role of malectin in Glc2Man9GlcNAc2-dependent quality control of α1-antitrypsin

نویسندگان

  • Yang Chen
  • Dan Hu
  • Rikio Yabe
  • Hiroaki Tateno
  • Sheng-Ying Qin
  • Naoki Matsumoto
  • Jun Hirabayashi
  • Kazuo Yamamoto
چکیده

Malectin was first discovered as a novel endoplasmic reticulum (ER)-resident lectin from Xenopus laevis that exhibits structural similarity to bacterial glycosylhydrolases. Like other intracellular lectins involved in glycoprotein quality control, malectin is highly conserved in animals. Here results from in vitro membrane-based binding assays and frontal affinity chromatography confirm that human malectin binds specifically to Glc(2)Man(9)GlcNAc(2) (G2M9) N-glycan, with a K(a) of 1.97 × 10(5) M(-1), whereas binding to Glc(1)Man(9)GlcNAc(2) (G1M9), Glc(3)Man(9)GlcNAc(2) (G3M9), and other N-glycans is barely detectable. Metabolic labeling and immunoprecipitation experiments demonstrate that before entering the calnexin cycle, the folding-defective human α1-antitrypsin variant null Hong Kong (AT(NHK)) stably associates with malectin, whereas wild-type α1-antitrypsin (AT) or N-glycan-truncated variant of AT(NHK) (AT(NHK)-Q3) dose not. Moreover, malectin overexpression dramatically inhibits the secretion of AT(NHK) through a mechanism that involves enhanced ER-associated protein degradation; by comparison, the secretion of AT and AT(NHK)-Q3 is only slightly affected by malectin overexpression. ER-stress induced by tunicamycin results in significantly elevated mRNA transcription of malectin. These observations suggest a possible role of malectin in regulating newly synthesized glycoproteins via G2M9 recognition.

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عنوان ژورنال:

دوره 22  شماره 

صفحات  -

تاریخ انتشار 2011