Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells

M'hamed Grati, Nisha Aggarwal, Emanuel E. Strehler, Robert J. Wenthold

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2995-3007
Number of pages13
JournalJournal of Cell Science
Volume119
Issue number14
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

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Calcium-Transporting ATPases
Cell Membrane
Membranes
Protein Isoforms
Stereocilia
Alternative Splicing
Inner Ear
Cytosol

Keywords

  • Alternative splicing
  • Inner ear explant
  • Intracellular loop
  • Leucine-isoleucine signal
  • Stereocilia

ASJC Scopus subject areas

  • Cell Biology

Cite this

Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells. / Grati, M'hamed; Aggarwal, Nisha; Strehler, Emanuel E.; Wenthold, Robert J.

In: Journal of Cell Science, Vol. 119, No. 14, 15.07.2006, p. 2995-3007.

Research output: Contribution to journalArticle

Grati, M'hamed ; Aggarwal, Nisha ; Strehler, Emanuel E. ; Wenthold, Robert J. / Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells. In: Journal of Cell Science. 2006 ; Vol. 119, No. 14. pp. 2995-3007.
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