Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells.
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.
Grati
M'hamed
M
Laboratory of Neurochemistry, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Aggarwal
Nisha
N
Strehler
Emanuel E
EE
Wenthold
Robert J
RJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002999:Clone Cells; D018076:DNA, Complementary / Q000302:isolation & purification; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D021381:Protein Transport; D051381:Rats; D013552:Swine
D018076:DNA, Complementary; D020033:Protein Isoforms; D007532:Isoleucine; D053499:Plasma Membrane Calcium-Transporting ATPases; D007930:Leucine