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Third-party-funded project

Title:
Regulation of the Na+-D-glucose cotransporter by protein RS1

Project management at the University of Würzburg:

• Prof. Dr. Hermann Koepsell

Participating scientists:

• Dr. Valentin Gorboulev
• Dr. Maike Veyhl

Abstract:
In this project we investigated the regulator protein RS1 that was firstly cloned by our group in 1992. RS1 is an intracellular protein that is transcribed by an intronless single copy gene. In the human this gene (RSC1A) is located on chromosome 1p36.1. We cloned RS1 from several species (pig, rabbit, mouse and man) and found that RS1 is expressed in epithelial cells of kidney and small intestine, in neurons, and in fat cells. RS1 is associated with the inner side of the plasma membrane. It contains consensus sequences for phosphorylation sites and for a ubiquitin associated domain that has been shown to be engaged in proteasomal protein degradation and in endocytosis. Performing coexpression experiments with RS1 and various plasma membrane transporters using Xenopus oocytes, we showed that RS1 regulates plasma membrane concentrations of a group of transporters independly of transcription. The Na+-D-glucose cotransporter SGLT1 belongs to this group of transporters. Employing an epithelial cell line we observed that RS1 can migrate into the nucleus where it inhibits the transcription of SGLT1. The regulator protein RS1 is supposed to coordinate short-term regulations of transporter concentrations within the plasma membrane with long-term transcriptional regulations of these transporters within the nucleus.

Key words:
    Regulator protein of plasma membrane transporters

Projekt period: from 01.2000 to 12.2002

Funding institution:
DFG ,Granting date: 22.11.1999

Preceding project:
SFB176 Teilprojekt A17

Publications:

• Reinhardt J, Veyhl M, Wagn K, Gambaryan S, Dekel C, Akhoundova A, Korn T, Koepsell H,. (1999). Cloning and characterization of the transport modifier RS1 from rabbit which was previously assumed to be specific for Na+-D-glucose cotransport. (monograph)
• Sauer GA, Nagel G, Koepsell H, Bamberg E, Hartung K,. (2000). Voltage and substrate dependence of the inverse transport mode of rabbit Na+/glucose cotransporter (SGLT1). (monograph)
• Seker H, Bertram B, Bürkle A, Kaina B, Pohl J, Koepsell H, Wießler M,. (2000). Mechanistic aspects of the cytotoxic activity of glufosfamide, a new tumour therapeutic agent. (monograph)
• Valentin M, Kühlkamp T, Wagner K, Krohne G, Arndt P, Baumgarten K, Weber W-M, Segal A, Veyhl M, Koepsell H,. (2000). The transport modifier RS1 is localized at the inner side of the plasma membrane and changes membrane capacitance. (monograph)
• Korn T, Kühlkamp T, Track C, Schatz I, Baumgarten K, Gorboulev V, Koepsell H,. (2001). The plasma membrane-associated protein RS1 decreases transcription of the transporter SGLT1 in confluent LLC-PK1 cells. (monograph)