M. Sahintoth et al., THE CLEAVED N-TERMINAL SIGNAL SEQUENCE OF THE CARDIAC NA-CA2+ EXCHANGER IS NOT REQUIRED FOR FUNCTIONAL MEMBRANE INTEGRATION(), Biochemical and biophysical research communications, 212(3), 1995, pp. 968-974
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.