Until now, dimerization of polytopic transmembrane proteins has been shown to occur by covalent and non-covalent interaction mainly through transmembrane domains. Covalent cysteine-based dimer formation has been extensively described for neurotransmitter transporters, such as the dopamine transporter, DAT and the glycine transporter as well as receptors. The fact that Benzethonium Chloride dimeric forms of ZnT3 were resistant to reducing agents and increased in response to oxidative stress, lead us to investigate tyrosine-mediated dimerization. Since its discovery 
in 1959, dityrosine formation has been described as a post-translational modification related with cellular stress and disease. Dityrosine modifications are produced in response to oxidative stress, aging, UV and c irradiation. Increased levels of dityrosine have been found in atheromatous plates, cataracts, acute inflammation, systemic bacterial infection and recently associated with a-synuclein fibrillogenesis and Ab amyloid oligomerization. Di-tyrosine formation as a normal post-translational modification has been described only in a limited group of structural proteins of the bacteria cell wall and insect ligaments, and in proteins of the extracellular matrix as collagen and elastin. Here we show tyrosine dimerization in a polytopic transmembrane protein, mediated by tyrosine residues in the carboxy terminal domain. In contrast to the described damage connotation and structural roles of dityrosine bonds, ZnT3 tyrosine modification presents a new functional paradigm for dityrosine bonds as regulators of both subcellular localization and metal transport activity. This ZnT3 posttranslational modification occurs spontaneously and it is regulated by oxidative stress. While SUMO is present throughout development, early Drosophila embryos contain particularly high concentrations of maternally contributed SUMO and the enzymes required for SUMO conjugation, suggesting that sumoylation may play particularly critical roles at this stage of fly development. Previous global analyses of SUMO substrates in S. cerevisiae and mammalian cultured cells have produced extensive lists of novel sumoylation targets. To date, however, there are no published studies that document the spectrum of sumoylated proteins in a specific developmental setting in a multicellular organism. To broaden our understanding of the function of sumoylation in early Drosophila development, we performed a mass spectrometrybased global identification of sumoylation targets in early embryos, and found over 140 direct sumoylation targets. Among the identified SUMO target proteins are players in many processes essential to embryonic development, including proteins involved in Ras signaling, cell cycle control, and embryonic patterning. To determine the functional significance of the identified sumoylated proteins, we carried out genetic, cell culture and immunolocalization studies, obtaining evidence for roles of SUMO in these same three processes. Thus, the proteomic, genetic, and cellular studies presented here all converge to suggest that SUMO Amikacin hydrate coordinates key aspects of early metazoan development. We observe diverse patterning defects among the sumo GLC embryos that developed a cuticle. In accordance with this observation, three absolutely critical patterning proteins, Dorsal, Bicoid, and Hunchback, are among the sumoylated proteins we detected in early embryo extracts. Previous studies have shown that sumoylation of Dorsal potentiates its activity during the immune response perhaps by making it a more potent transcriptional activator.