Sodium-coupled transporters for Krebs cycle intermediates

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Physiology

Background:

• Krebs cycle intermediates are transported across cell membranes by secondary active transporters.
• These transporters utilize sodium gradients for substrate uptake, suggesting multiple Na+/dicarboxylate cotransporter proteins exist.
• Previous functional studies indicated the presence of at least three or more Na+/dicarboxylate cotransporter proteins per species.

Purpose of the Study:

• To identify and characterize cDNAs encoding Na+/dicarboxylate cotransporters.
• To understand the molecular basis of dicarboxylate transport in kidney and other tissues.
• To investigate the structural and functional relationships within the Na+/dicarboxylate cotransporter gene family.

Main Methods:

• Isolation and sequencing of cDNAs from rabbit, human, and rat kidney.
• Functional characterization of identified transporters in membrane vesicles and cells.
• Bioinformatic analysis to predict secondary structure and identify related transporters.

Main Results:

• Several cDNAs, designated NaDC-1, were isolated, coding for low-affinity Na+/dicarboxylate cotransporters.
• NaDC-1 transporters are part of a distinct gene family, including renal and intestinal Na+/sulfate cotransporters.
• A secondary structure model for NaDC-1 predicts 11 transmembrane domains and an extracellular N-glycosylated carboxy terminus.

Conclusions:

• NaDC-1 represents a key molecular entity for dicarboxylate transport in the kidney.
• The Na+/dicarboxylate cotransporter family exhibits diverse substrate specificities and tissue distributions.
• Understanding these transporters is crucial for comprehending cellular metabolism and nutrient transport.