N-glycosylation analysis of the human Tweety family of putative chloride ion channels supports a penta-spanning membrane arrangement: impact of N-glycosylation on cellular processing of Tweety homologue 2 (TTYH2)
He, Yaowu, Ramsay, Andrew J., Hunt, Melanie L., Whitbread, Astrid K., Myers, Stephen A., & Hooper, John D. (2008) N-glycosylation analysis of the human Tweety family of putative chloride ion channels supports a penta-spanning membrane arrangement: impact of N-glycosylation on cellular processing of Tweety homologue 2 (TTYH2). Biochemical Journal, 412(1), pp. 45-55.
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The Tweety proteins are a family of recently identified putative Cl(-) channels predicted to be modified by N-glycosylation and, controversially, to contain five or six membrane-spanning domains, leading to the contentious proposal that members of this family do not share the same topology at the plasma membrane. In humans, three family members have been identified, designated TTYH1 (Tweety homologue 1), TTYH2 and TTYH3. To gain greater insight into the arrangement of membrane-spanning domains and cellular processing of Tweety proteins, in the present study we have examined the sequence homology, hydrophobicity and N-glycan content of members of this family and performed N-glycosylation site-mutagenesis studies on TTYH2 and TTYH3. Based on these observations we propose a structure for Tweety family proteins which incorporates five membrane-spanning domains with a topology at the cell surface in which the N-terminus is located extracellularly and the C-terminus cytoplasmically. Our results also suggest that N-glycosylation is important, but not essential, in the processing of members of the Tweety family with results indicating that, although incomplete N-glycosylation mediates reduced expression and increased ubiquitination of TTYH2, N-glycosylation is not the determining factor for TTYH2 trafficking to the plasma membrane. This information will be important for the characterization of Tweety family proteins in normal physiology and disease.
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|Item Type:||Journal Article|
|Additional Information:||For more information, please refer to the journal's website (see hypertext link) or contact the author.|
|Keywords:||Ion channel, TTYH2, Kidney|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Receptors and Membrane Biology (060110)|
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Science and Technology|
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > School of Life Sciences
|Copyright Owner:||Copyright 2008 (The authors); Exclusive licence to publish - Portland Press|
|Deposited On:||04 Feb 2009 11:03|
|Last Modified:||29 Feb 2012 23:51|
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