Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it

Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it
Title:
Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it
Other Titles:
Cell Cycle
Publication Date:
08 February 2017
Citation:
Wai-Heng Lua, Wei-Li Ling, Chinh Tran-To Su, Joshua Yi Yeo, Chandra Shekhar Verma, Birgit Eisenhaber, Frank Eisenhaber & Samuel Ken-En Gan (2017) Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it, Cell Cycle, 16:5, 457-467, DOI: 10.1080/15384101.2017.1281480
Abstract:
The IgA receptor, Fcar (CD89) consists of 5 sequence segments: 2 segments (S1, S2) forming the potential signal peptide, 2 extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain. Despite possessing the complete signal peptide S1+S2, the variant APD is only found in the intracellular space whereas the wild-type variant 1 is efficiently secreted and variant 4 leaks to the extracellular space. Further mutational experiments involving signal peptide replacements, cleavage site modifications, and studies on alternative isoforms demonstrate that despite the completeness of the signal peptide motif, the presence of the EC1 domain is essential for efficient extracellular export.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This work was supported by the JCO1334i00050 grant from Joint Council Office, Agency for Science, Technology, and Research (ASTAR) in Singapore.
Description:
ISSN:
1538-4101
1551-4005
Files uploaded:

File Size Format Action
826-discovery-of-a-novel-splice-variant.pdf 1.15 MB PDF Open