Characterization of a regulatory region in the N-terminus of rabbit kv1.3.
The N-terminus of rabbit Kv1.3 contains a signal sequence which regulates expression of Kv1.3 proteins in the plasma membrane. Removal of an N-terminal region (aa3-39) produced an increase in expressed K+ current. Progressive deletion at the N-terminus demonstrated that the shortest deletion required for the elevation of K current is D6-34. Since the functional signal sequence must include both ends of the peptide segment aa6-34 where charged residues are densely distributed, it is conceivable that this N-terminal signal sequence is related to charge or its associated hydrophilicity. Removal of two charged residues (31R, 33E) through amino acid substitution which converts deletion construct D3-27 to D3-27* effectively raises the amplitude of expressed current, further indicating the importance of charged residues. With the use of a mutated dynamin and a soluble N-terminal peptide, we also revealed that the N-terminal signal sequence may not act through the endocytotic pathway.
Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
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D000595:Amino Acid Sequence; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D034281:Dynamins; D004553:Electric Conductivity; D004705:Endocytosis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000494:pharmacology; D017353:Gene Deletion; D015870:Gene Expression; D051664:Kv1.3 Potassium Channel; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009865:Oocytes; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D021382:Protein Sorting Signals / Q000737:chemistry; D018075:RNA, Complementary / Q000235:genetics; D011817:Rabbits; D013329:Structure-Activity Relationship; D014162:Transfection; D014982:Xenopus laevis
D051664:Kv1.3 Potassium Channel; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021382:Protein Sorting Signals; D018075:RNA, Complementary; D020558:GTP Phosphohydrolases; D034281:Dynamins