REVIEW

The Sac domain-containing phosphoinositide phosphatases: structure, function, and disease

  • FoSheng HSU ,
  • Yuxin MAO
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  • Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA

Received date: 02 Nov 2012

Accepted date: 04 Feb 2013

Published date: 01 Aug 2013

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Phosphoinositides (PIs) have long been known to have an essential role in cell physiology. Their intracellular localization and concentration must be tightly regulated for their proper function. This spatial and temporal regulation is achieved by a large number of PI kinases and phosphatases that are present throughout eukaryotic species. One family of these enzymes contains a conserved PI phosphatase domain termed Sac. Although the Sac domain is homologous among different Sac domain-containing proteins, all appear to exhibit varied substrate specificity and subcellular localization. Dysfunctions in several members of this family are implicated in a range of human diseases such as cardiac hypertrophy, bipolar disorder, Down’s syndrome, Charcot-Marie-Tooth disease (CMT) and Amyotrophic Lateral Sclerosis (ALS). In plant, several Sac domain-containing proteins have been implicated in the stress response, chloroplast function and polarized secretion. In this review, we focus on recent findings in the family of Sac domain-containing PI phosphatases in yeast, mammal and plant, including the structural analysis into the mechanism of enzymatic activity, cellular functions, and their roles in disease pathophysiology.

Cite this article

FoSheng HSU , Yuxin MAO . The Sac domain-containing phosphoinositide phosphatases: structure, function, and disease[J]. Frontiers in Biology, 2013 , 8(4) : 395 -407 . DOI: 10.1007/s11515-013-1258-y

Acknowledgements

This work is supported by grants from NIH: 1R01GM094347 (to Y.M.) and is funded by the Cornell University Harry Samuel Mann Award (to F.H.).
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