期刊
JOURNAL OF CELL SCIENCE
卷 119, 期 14, 页码 2995-3007出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.03030
关键词
alternative splicing; inner ear explant; intracellular loop; leucine-isoleucine signal; stereocilia
类别
资金
- Intramural NIH HHS Funding Source: Medline
- NIGMS NIH HHS [GM 28835] Funding Source: Medline
The plasma membrane Ca2+-ATPase-2 (PMCA2) is expressed in stereocilia of hair cells of the inner ear, whereas PMCA1 is expressed in the basolateral plasma membrane of hair cells. Both extrude excess Ca2+ from the cytosol. They are predicted to contain ten membrane-spanning segments, two large cytoplasmic loops as well as cytosolic N- and C-termini. Several isoform variants are generated for both PMCA1 and PMCA2 by alternative splicing, affecting their first cytosolic loop (A-site) and their C-terminal tail. To understand how these isoforms are differentially targeted in hair cells, we investigated their targeting regions and expression in hair cells. Our results show that a Leu-Ile motif in 'b'-tail splice variants promotes PMCA1b and PMCA2b basolateral sorting in hair cells. Moreover, apical targeting of PMCA2 depends on the size of the A-site-spliced insert, suggesting that the conformation of the cytoplasmic loop plays a role in apical targeting.
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