THE CLEAVED N-TERMINAL SIGNAL SEQUENCE OF THE CARDIAC NA-CA2+ EXCHANGER IS NOT REQUIRED FOR FUNCTIONAL MEMBRANE INTEGRATION()

The cardiac Na+-Ca2+ exchanger differs from most other polytopic membr ane proteins in that the amino terminus is cleaved during integration into the endoplasmic reticulum membrane. In this study, the cleaved N- terminal signal sequence of the exchanger was deleted (DelSS) or rende red uncleavable by mutation of the cleavage site (MutSS). Functional a nalysis of the mutants expressed in Xenopus laevis oocytes and sf9 ins ect cells demonstrates that DelSS exchanger catalyzes Na+-dependent Ca 2+ transport at wild-type levels, while activity of MutSS exchanger is reduced to approximately 60% of wild-type in oocytes and 20% in sf9 c ells. These results indicate that neither the presence nor the cleavag e of the signal peptide is required for functional assembly of the exc hanger protein in the membrane. Furthermore, these observations suppor t the concept that internal topogenic signals play the major role in m embrane insertion of the Na+-Ca2+ exchanger. (C) 1995 Academic Press, Inc.