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Unlocking therapeutic potential of SLC13 transporters

Date:
June 18, 2014
Source:
The Rockefeller University Press
Summary:
The first functional analysis of a member of a family of transporter proteins implicated in diabetes, obesity, and lifespan, has been completed, potentially providing the key that will enable researchers to unlock their therapeutic potential. Members of the SLC13 transporter family play a key role in the regulation of fat storage, insulin resistance, and other processes.
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Researchers analyzed the functional properties of VcINDY (pictured), laying the groundwork for future studies of a family of transporters implicated in diabetes, obesity, and lifespan.
Credit: Mulligan et al., 2014; structure from Protein Data Bank accession no. 4F35

Researchers have provided the first functional analysis of a member of a family of transporter proteins implicated in diabetes, obesity, and lifespan. The study appears in the June issue of The Journal of General Physiology.

Members of the SLC13 transporter family play a key role in the regulation of fat storage, insulin resistance, and other processes. Some SLC13 transporters mediate the transport of Krebs cycle intermediates -- compounds essential for the body's metabolic activity -- across the cell membrane. Previous studies have shown that loss of one member of this family protects mice against obesity and insulin resistance, and loss of another results in reduced fat storage and extended lifespan in fruit flies. These findings hint at the therapeutic potential of targeting these transporters to combat metabolic disease, obesity, diabetes, and other conditions.

A recently obtained high-resolution structure of VcINDY -- a member of the SLC13 family found in the bacteria that causes cholera -- has provided key structural insights, but understanding how these transporters function at the cellular level remains a mystery. To find out more, researchers from the National Institute of Neurological Disorders and Stroke (NINDS) reconstituted VcINDY into small synthetic vesicles called liposomes that allowed them to monitor its activity in isolation. Led by Joseph Mindell, the team was thereby able to analyze the properties of VcINDY as a transporter and provide a model that lays the groundwork for future studies of SLC13 transporters, potentially providing the key that will enable researchers to unlock their therapeutic potential.


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The above post is reprinted from materials provided by The Rockefeller University Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. C. Mulligan, G. A. Fitzgerald, D.-N. Wang, J. A. Mindell. Functional characterization of a Na -dependent dicarboxylate transporter from Vibrio cholerae. The Journal of General Physiology, 2014; 143 (6): 745 DOI: 10.1085/jgp.201311141

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The Rockefeller University Press. "Unlocking therapeutic potential of SLC13 transporters." ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618135838.htm>.
The Rockefeller University Press. (2014, June 18). Unlocking therapeutic potential of SLC13 transporters. ScienceDaily. Retrieved July 28, 2015 from www.sciencedaily.com/releases/2014/06/140618135838.htm
The Rockefeller University Press. "Unlocking therapeutic potential of SLC13 transporters." ScienceDaily. www.sciencedaily.com/releases/2014/06/140618135838.htm (accessed July 28, 2015).

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