More than hemoglobin - the unexpected diversity of globins in vertebrate red blood cells.

Miriam Götting,Mikko Nikinmaa

doi:10.14814/phy2.12284

Abstract

In many multicellular organisms, oxygen is transported by respiratory proteins, which are globins in vertebrates, between respiratory organs and tissues. In jawed vertebrates, eight globins are known which are expressed in a highly tissue-specific manner. Until now, hemoglobin (Hb) had been agreed to be the only globin expressed in vertebrate erythrocytes. Here, we investigate for the first time the mRNA expression of globin genes in nucleated and anucleated erythrocytes of model vertebrate species by quantitative real-time reverse transcription PCR (qRT-PCR). Surprisingly, we found transcripts of the whole gnathostome globin superfamily in RBCs. The mRNA expression levels varied among species, with Hb being by far the dominant globin. Only in stickleback, a globin previously thought to be neuron-specific, neuroglobin, had higher mRNA expression. We furthermore show that in birds transcripts of globin E, which was earlier reported to be transcribed only in the eye, are also present in RBCs. Even in anucleated RBCs of mammals, we found transcripts of myoglobin, neuroglobin, and cytoglobin. Our findings add new aspects to the current knowledge on the expression of globins in vertebrate tissues. However, whether or not the mRNA expression of these globin genes has any functional significance in RBCs has to be investigated in future studies.

Highlights

Respiratory proteins, globins in vertebrates, increase the efficiency of oxygen storage and transport since many multicellular organisms cannot obtain enough oxygen to sustain active metabolism by diffusion (Hardison 1996)
89 211 144 153 104 177 145 133 160 199 125 154 122 128 128 known teleost globin genes are transcribed in red blood cells (RBC)
The Ngb gene was transcribed in RBCs at even a higher level than hemoglobin a (Hba) and showed the highest copy numbers of all stickleback tissues

Summary

Introduction

Respiratory proteins, globins in vertebrates, increase the efficiency of oxygen storage and transport since many multicellular organisms cannot obtain enough oxygen to sustain active metabolism by diffusion (Hardison 1996). Globins are well-characterized proteins and used as models for investigating mechanisms of protein evolution, structure, and function (e.g., Dickerson and Geis 1983; Hardison 2012) In vertebrates, they are molecules of 16– 23 kDa with a heme prosthetic group, by which they reversibly bind O2 and other gaseous ligands. Globins are expressed in a highly species- and tissue-specific manner and have putatively divergent functions (recently reviewed in Burmester and Hankeln 2014). They are all putatively involved in cellular processes related to O2 transport and storage, detoxification of reactive oxygen and nitrogen species, sensing and signaling (Vinogradov and Moens 2008) or may have yet unknown functions.

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