Functional organization of cytoplasmic portals controlling access to the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel pore

The Journal of Biological Chemistry
Man-Song LiP Linsdell

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel that apparently has evolved from an ancestral active transporter. Key to the CFTR's switch from pump to channel function may have been the appearance of one or more "lateral portals." Such portals connect the cytoplasm to the transmembrane channel pore, allowing a continuous pathway for the electrodiffusional movement of Cl- ions. However, these portals remain the least well-characterized part of the Cl- transport pathway; even the number of functional portals is uncertain, and if multiple portals do exist, their relative functional contributions are unknown. Here, we used patch-clamp recording to identify the contributions of positively charged amino acid side chains located in CFTR's cytoplasmic transmembrane extensions to portal function. Mutagenesis-mediated neutralization of several charged side chains reduced single-channel Cl- conductance. However, these same mutations differentially affected channel blockade by cytoplasmic suramin and Pt(NO2)42- anions. We considered and tested several models by which the contribution of these positively charged side chains to one or more independent or non-independent portals to the pore could affect Cl- co...Continue Reading

References

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Dec 15, 2015·Cellular and Molecular Life Sciences : CMLS·Yassine El HianiPaul Linsdell
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Oct 5, 2016·Cellular and Molecular Life Sciences : CMLS·Paul Linsdell
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Citations

Jul 4, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gwenaëlle ConseilSusan P C Cole
Mar 28, 2018·The Journal of General Physiology·Tzyh-Chang HwangSamantha Destefano
May 21, 2018·Cellular and Molecular Life Sciences : CMLS·Brice HoffmannIsabelle Callebaut
Jan 2, 2020·Cell Biochemistry and Biophysics·Paul LinsdellYassine El Hiani
Jan 17, 2020·Microbiology and Molecular Biology Reviews : MMBR·Paul Blount, Irene Iscla
Oct 4, 2018·Biochemistry·Jonathan F FayJames Z Chen
Oct 15, 2021·The Journal of General Physiology·Daniel T InfieldNael A McCarty

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