Mutational analyses of the signals involved in the subcellular location of DSCR1

Sandra Cristina Pfister¹ , Gláucia Maria Machado-Santelli² , Sang Won Han³ and Flávio Henrique-Silva¹

¹Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luiz km 235, São Carlos 13565-905, SP, Brazil

²Department of Histology and Embryology, Institute of Biomedical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 1524, São Paulo 05508-900, SP, Brazil

³Department of Biophysics, Federal University of São Paulo, Rua Botucatu 862, São Paulo 04023-062, SP, Brazil

author email corresponding author email

BMC Cell Biology 2002, 3:24doi:10.1186/1471-2121-3-24


Published:	11 September 2002

Abstract

Background

Down syndrome is the most frequent genetic disorder in humans. Rare cases involving partial trisomy of chromosome 21 allowed a small chromosomal region common to all carriers, called Down Syndrome Critical Region (DSCR), to be determined. The DSCR1 gene was identified in this region and is expressed preferentially in the brain, heart and skeletal muscle. Recent studies have shown that DSCR1 belongs to a family of proteins that binds and inhibits calcineurin, a serine-threonine phosphatase. The work reported on herein consisted of a study of the subcellular location of DSCR1 and DSCR1-mutated forms by fusion with a green fluorescent protein, using various cell lines, including human.

Results

The protein's location was preferentially nuclear, independently of the isoform, cell line and insertion in the GFP's N- or C-terminal. A segment in the C-terminal, which is important in the location of the protein, was identified by deletion. On the other hand, site-directed mutational analyses have indicated the involvement of some serine and threonine residues in this event.

Conclusion

In this paper, we discuss the identification of amino acids which can be important for subcellular location of DSCR1. The involvement of residues that are prone to phosphorylation suggests that the location and function of DSCR1 may be regulated by kinases and/or phosphatases.