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Open Access Research

ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons

Jin-A Lee1*, Lei Liu2, Robyn Javier2, Anatol C Kreitzer2, Celine Delaloy2 and Fen-Biao Gao3*

Author Affiliations

1 Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811, Korea

2 Gladstone Institute of Neurological Disease, San Francisco, California, 94158 USA

3 Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, 01605 USA

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Molecular Brain 2011, 4:37  doi:10.1186/1756-6606-4-37

Published: 5 October 2011

Abstract

Backgrounds

Endosomal sorting complex required for transport (ESCRT) is involved in several fundamental cellular processes and human diseases. Many mammalian ESCRT proteins have multiple isoforms but their precise functions remain largely unknown, especially in human neurons.

Results

In this study, we differentiated human embryonic stem cells (hESCs) into postmitotic neurons and characterized the functional properties of these neurons. Moreover, we found that among the three human paralogs of the yeast ESCRT-III subunit Snf7, hSnf7-1 and hSnf7-2 are most abundantly expressed in human neurons. Both hSnf7-1 and hSnf7-2 are required for the survival of human neurons, indicating a non-redundant essential function. Indeed, hSnf7-1 and hSnf7-2 are preferentially associated with CHMP2A and CHMP2B, respectively, and regulate the turnover of distinct transmembrane cargos such as neurotransmitter receptors in human neurons.

Conclusion

These findings indicate that different mammalian paralogs of the yeast ESCRT-III subunit Snf7 have non-redundant functions in human neurons, suggesting that ESCRT-III with distinct subunit compositions may preferentially regulate different cargo proteins.

Keywords:
human embryonic stem cells; neurons; ESCRT; CHMP2B; Snf7