Function and presumed molecular structure of Na(+)-D-glucose cotransport systems.

Functional characterization of Na(+)-D-glucose cotransport in intestine and kidney indicates the existence of heterogeneous Na(+)-D-glucose cotransport systems. Target size analysis of the transporting unit and model analysis of substrate binding have been performed and proteins have been cloned which mediate (SGLT1) and modulate (RS1) the expression of Na(+)-D-glucose cotransport. The experiments support the hypothesis that functional Na(+)-D-glucose cotransport systems in mammals are composed of two SGLT1-type subunits and may contain one or two RS1-type proteins. SGLT1 contains up to twelve membrane-spanning alpha-helices, whereas RS1 is a hydrophilic extracellular protein which is anchored in the brush-border membrane by a hydrophobic alpha-helix at the C-terminus. SGLT1 alone is able to translocate glucose together with sodium; however, RS1 increases the Vmax of transport expressed by SGLT1. In addition, the biphasic glucose dependence of transport, which is typical for kidney and has been often observed in intestine, was only obtained after coexpression of SGLT1 and RS1.