Abstract

Collectin liver 1 (CL-L1, alias CL-10) and collectin kidney 1 (CL-K1, alias CL-11), encoded by the COLEC10 and COLEC11 genes, respectively, are highly homologous soluble pattern recognition molecules in the lectin pathway of complement. These proteins may be involved in anti-microbial activity and in tissue development as mutations in COLEC11 are one of the causes of the developmental defect syndrome 3MC. We studied variations in COLEC10 and COLEC11, the impact on serum concentration and to what extent CL-L1 and CL-K1 serum concentrations are correlated. We sequenced the promoter regions, exons and exon-intron boundaries of COLEC10 and COLEC11 in samples from Danish Caucasians and measured the corresponding serum levels of CL-L1 and CL-K1. The median concentration of CL-L1 and CL-K1 was 1.87 μg/ml (1.00–4.14 μg/ml) and 0.32 μg/ml (0.11–0.69 μg/ml), respectively. The level of CL-L1 strongly correlated with CL-K1 (ρ = 0.7405, P <0.0001). Both genes were highly conserved with the majority of variations in the non-coding regions. Three non-synonymous variations were tested: COLEC10 Glu78Asp (rs150828850, minor allele frequency (MAF): 0.003), COLEC10 Arg125Trp (rs149331285, MAF: 0.007) and COLEC11 His219Arg (rs7567833, MAF: 0.033). Carriers of COLEC10 Arg125Trp had increased CL-L1 serum levels (P = 0.0478), whereas promoter polymorphism COLEC11-9570C>T (rs3820897) was associated with decreased levels of CL-K1 (P = 0.044). In conclusion, COLEC10 and COLEC11 are highly conserved, which may reflect biological importance of CL-L1 and CL-K1. Moreover, the strong inter individual correlation between the two proteins suggests that a major proportion are found as heterooligomers or subjected to the same regulatory mechanisms.

Highlights

  • Collectins are C-type lectins, a family of pattern recognition molecules involved in innate immunity

  • The Glu78Asp variation in exon 3 occurs in a variable residue and was predicted to be benign, in contrast to Arg125Trp in exon 6, which is located in an evolutionary constrained position in the neck domain and was by in silico analysis predicted to be potentially critical for the structure (Table 4)

  • To study how the genetic variation affects structure and concentrations in the background population we examined the COLEC10 and COLEC11 in healthy individuals and determined the circulating levels of CL-L1 and CL-K1 in corresponding serum samples

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Summary

Introduction

Collectins are C-type lectins, a family of pattern recognition molecules involved in innate immunity. The polypeptide chains are composed of a collagen-like region, an alpha helical neck domain and a carbohydrate recognition domain (CRD). More recently described collectins comprises CLL1 (alias collectin-10, collectin liver 1 or CL-10) [3], CL-K1 (alias collectin-11, collectin kidney 1 or CL-11) [4], and CL-P1 (alias collectin-12, collectin placenta 1, CL-12 or SRCL). Both CLL1 and CL-K1 are soluble molecules that have been found circulating in blood in complex with lectin complement pathway associated serine proteases (MASPs) [5,6,7,8]. MASP1 and MASP2, encode MASP-1/-3 (alias MASP1 isoform 1 and 2) and MASP-2 (alias MASP2 isoform 1), respectively, and encode the alternatively spliced non-catalytic products, MAP-1 (alias MAp44 or MASP1 isoform 3) and sMAP (alias MAp19, MAP-2 or MASP2 isoform 2), respectively [9]

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