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Kv1.3 Contains an Alternative C-Terminal ER Exit Motif and is Recruited into COPII Vesicles by Sec24a

Title: Kv1.3 Contains an Alternative C-Terminal ER Exit Motif and is Recruited into COPII Vesicles by Sec24a.
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Name(s): Stagg, Scott, author
Spear, John M., author
Koborssy, Dolly Al, author
Schwartz, Austin B, author
Johnson, Adam J, author
Audhya, Anjon, author
Fadool, Debra A, author
Type of Resource: text
Genre: Text
Date Issued: 2015-07-10
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Background Potassium channels play a fundamental role in resetting the resting membrane potential of excitable cells. Determining the intracellular trafficking and localization mechanisms of potassium channels provides a platform to fully characterize their maturation and functionality. Previous investigations have discovered residues or motifs that exist in their primary structure, which directly promote anterograde trafficking of nascent potassium channels. Recently, a non-conical di-acidic motif (E483/484) has been discovered in the C-terminus of the mammalian homologue of the Shaker voltage-gated potassium channel subfamily member 3 (Kv1.3), and was shown to disrupt the anterograde trafficking of Kv1.3. Results We have further investigated the intracellular trafficking requirements of Kv1.3 both in vivo and in vitro. First, three alternative C-terminal acidic residues, E443, E445, E447 were probed for their involvement within the early secretory pathway of Kv1.3. Single point (E443A, E445A, and E447A) and double point (E443A-E445A, E445A-E447A) mutations exhibited no significant changes in their endoplasmic reticulum (ER) retention. The triple point mutant E443A-E445A-E447A displayed a modest ER retention while deletion of the C-terminus showed dramatic ER retention. Second, we demonstrate in vivo the requirement for the Sec24a isoform to confer anterograde trafficking using a siRNA knockdown assay. Third, we show in vitro the association of recombinantly expressed Kv1.3 and Sec24a proteins. Conclusion These results expand upon previous studies aimed at deciphering the Kv1.3 secretory trafficking mechanisms and further show in vitro evidence of the association between Kv1.3 and the COPII cargo adaptor subunit isoform Sec24a.
Identifier: FSU_libsubv1_scholarship_submission_1475170159 (IID), 10.1186/s12858-015-0045-6 (DOI)
Keywords: Early secretory pathway, Anterograde intracellular trafficking, COPII, Endoplasmic reticulum, Voltage-gated potassium channel, Di-acidic motif, siRNA
Publication Note: Publisher's Version also Available at http://bmcbiochem.biomedcentral.com/articles/10.1186/s12858-015-0045-6
Preferred Citation: Spear, J. M., Koborssy, D. A., Schwartz, A. B., Johnson, A. J., Audhya, A., Fadool, D. A., & Stagg, S. M. (2015). Kv1. 3 contains an alternative C-terminal ER exit motif and is recruited into COPII vesicles by Sec24a. BMC biochemistry, 16(1), 16.
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1475170159
Owner Institution: FSU
Is Part Of: BioMed Central Biochemistry.
Issue: iss. 16, vol. 16

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Stagg, S., Spear, J. M., Koborssy, D. A., Schwartz, A. B., Johnson, A. J., Audhya, A., & Fadool, D. A. (2015). Kv1.3 Contains an Alternative C-Terminal ER Exit Motif and is Recruited into COPII Vesicles by Sec24a. Biomed Central Biochemistry. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1475170159