Sumoylation in the developing neural tube

Abstract

Proliferation and differentiation are critical processes during development. In this context, the developing neural tube is a major field of study due to potential application of the obtained results in the treatment of central nervous system lesions and neurodegenerative diseases. The understanding of the involved mechanisms depends on the identification and characterization of the regulatory events and signaling pathways that lead to the correct progression of development. A signaling system that increases its relevance, specially concerning transcriptional regulation, is the protein modification by SUMO. SUMO (Small Ubiquitin-like MOdifier) is a small polypeptide, similar to ubiquitin, attaching covalently to other proteins as a post-translational modifier. The modification process shares several similarities with ubiquitination, as the presence of an activating E1 enzyme and a conjugating E2 enzyme, which transfers SUMO to the target protein. In most of the cases, this process is facilitated by an E3 ligase. To this point, the family of proteins PIAS has been widely studied. Sumoylation has been related to transcriptional regulation, nucleus-cytoplasm transport, genomic and protein stability and enzymatic modulation. In the neural landscape, modification by SUMO has been studied in synapses and neurodegenerative diseases, but a role in neural development is still unclear. Taking into consideration that SUMO modification is essential in eukaryotes and relevant for transcriptional regulation and many other functions, its implication in neural development is needed. In this work, we have investigated the role of sumoylation during the development of the vertebrate central nervous system by electroporation of SUMO molecules and ligases of the PIAS family.