Structure of Na-<i>D</i>-Glucose Cotransport Systems

Abstract

Functional characterization of Na⁺-<i>D</i>-glucose cotransport and the analysis of genetic diseases indicate heterogeneous Na⁺-<i>D</i>-glucose cotransport systems in the intestine and in various regions of the kidney. Target size analysis of the transporting unit and model analysis of phlorizin binding to the transporter suggest that the transport systems have a molecular mass around 300,000 daltons and contain two coexisting transport sites. Two types of proteins are thought to be components of Na⁺-<i>D</i>-glucose cotransport systems: A membrane protein with up to 12 membrane-spanning α-helices (SGLT1) which has been cloned from intestine and is also found in kidney, and a membrane-associated extracellular protein (RS1) which has been cloned from kidney and is also present in intestine. RS1 is anchored in the brush-border membrane by a hydrophobic α-helix at the C-terminus. SGLT1 alone is able to translocate glucose together with sodium; however, RS1 increases the V_max of the uptake expressed by SGLT1. In addition, the biphasic glucose dependence of transport which is typical for kidney and has also been observed in intestine, was only obtained after the coexpression of both SGLT1 and RS1. The data support the hypothesis that Na⁺-<i>D</i>-glucose cotransport systems are composed of two SGLT1-type and one or two RS1-type proteins.