Sialylation in protostomes: a perspective from Drosophila genetics and biochemistry

Abstract

Numerous studies have revealed important functions for sialylation in both prokaryotes and higher animals. However, the genetic and biochemical potential for sialylation in Drosophila has only been confirmed recently. Recent studies suggest significant similarities between the sialylation pathways of vertebrates and insects and provide evidence for their common evolutionary origin. These new data support the hypothesis that sialylation in insects is a specialized and developmentally regulated process which likely plays a prominent role in the nervous system. Yet several key issues remain to be addressed in Drosophila, including the initiation of sialic acid de novo biosynthesis and understanding the structure and function of sialylated glycoconjugates. This review discusses our current knowledge of the Drosophila sialylation pathway, as compared to the pathway in bacteria and vertebrates. We arrive at the conclusion that Drosophila is emerging as a useful model organism that is poised to shed new light on the function of sialylation not only in protostomes, but also in a larger evolutionary context.

N-Glycosylation in Regulation of the Nervous System

“…As a result, they can only be unambiguously detected and analyzed by the most sensitive glycomic approaches, such as multidimensional mass spectrometry (Aoki et al 2007, Koles et al 2007). Despite the fact that sialylation is so scarce, it has a prominent function in the nervous system of Drosophila , which was revealed by analysis of mutant phenotypes of the Drosophila sialyltransferase ( DSiaT ) and CMP-sialic acid synthetase ( CSAS ) genes that play key roles in the sialylation pathway (Koles et al 2009). Unlike mammalian organisms that have twenty different sialyltransferases, Drosophila possesses only one sialyltransferase, DSiaT, which significantly simplifies the in vivo analysis of sialylation functions (Koles et al 2009).…”

“…Despite the fact that sialylation is so scarce, it has a prominent function in the nervous system of Drosophila , which was revealed by analysis of mutant phenotypes of the Drosophila sialyltransferase ( DSiaT ) and CMP-sialic acid synthetase ( CSAS ) genes that play key roles in the sialylation pathway (Koles et al 2009). Unlike mammalian organisms that have twenty different sialyltransferases, Drosophila possesses only one sialyltransferase, DSiaT, which significantly simplifies the in vivo analysis of sialylation functions (Koles et al 2009). DSiaT shows a close evolutionary relationship to the ST6Gal family of mammalian sialyltransferases; it modifies glycoproteins by attaching α 2,6 -linked sialic acids to LacNAc termini of N-glycans (Koles et al 2004, Repnikova et al 2010).…”

Molecular Phylogeny and Functional Genomics of β-Galactoside α2,6-Sialyltransferases That Explain Ubiquitous Expression of st6gal1 Gene in Amniotes

“…Given the small number of invertebrate genomes explored so far, the information available in protostomes and deuterostomes is quite fragmentary and has been mainly documented in Drosophila and vertebrates. Sialylation in insects has long been controversial (32,35,77), and recently, DSiaT, a unique st6gal gene, has been characterized in Drosophila (31). It is exclusively expressed in a subset of neurons in late embryonic stage 17, in the optic lobe of third instar larva and in the region of olfactory projection neurons in adult head (35).…”

“…Sialylation in insects has long been controversial (32,35,77), and recently, DSiaT, a unique st6gal gene, has been characterized in Drosophila (31). It is exclusively expressed in a subset of neurons in late embryonic stage 17, in the optic lobe of third instar larva and in the region of olfactory projection neurons in adult head (35). The encoded enzyme was found to be involved in the function of a voltage-gated sodium channel and neuromuscular junction and appears to be .…”

“…Furthermore, a ST6Gal cDNA named DSiaT was cloned from Drosophila melanogaster (31), suggesting that the ST6Gal family was present in insects, although not much Neu5Ac could be detected (32)(33)(34). DSiaT is detected almost exclusively in central nervous system (CNS) neurons in the embryonic stage 17, in the optic lobe of third instar larva, and in adult head (35). Targeted disruption of the DSiaT gene results in a neurological phenotype, suggesting that DSiaT modulates the nervous system function of voltage-gated sodium channel (36).…”