Synergism of shrew-1's signal peptide and transmembrane segment required for plasma membrane localization.
Signal peptides (SP) and transmembrane segments (TMS) ensure proper subcellular targeting and localization of proteins. Thus, understanding the molecular variability of this targeting information is essential. In this study, we functionally analyzed the predicted SP and the TMS of adherens junction protein, shrew-1 (Bharti et al. Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells. Mol Biol Cell 2004:15:397). We used human secreted alkaline phosphatase (SEAP) as reporter protein. The SP of shrew-1 was able to functionally substitute for SEAP's intrinsic SP and was cleaved, indicating that it acts as a start-transfer signal and not a signal anchor. In turn, the TMS of shrew-1 functions as stop-transfer signal. Notably, clearly detectable plasma membrane localization is only achieved when the fusion protein contains both the SP and the TMS of shrew-1. In combination with the intrinsic SP from SEAP, the shrew-1 TMS is unable to promote stable plasma membrane localization. Hence, it may be assumed that this synergism between an SP and a TMS to mediate plasma membrane localization is essential for structural and/or functional integrity of shrew-1.
Resch
Eduard
E
Department of Molecular Cell Biology and Human Genetics, Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, Frankfurt am Main, Germany.
Quaiser
Saskia
S
Quaiser
Tom
T
Schneider
Gisbert
G
Starzinski-Powitz
Anna
A
Schreiner
Alexander
A
D000469:Alkaline Phosphatase / Q000378:metabolism; D000595:Amino Acid Sequence; D001692:Biological Transport; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
C483313:AJAP1 protein, human; D015815:Cell Adhesion Molecules; D021382:Protein Sorting Signals; D000469:Alkaline Phosphatase