Dynamic localization of the Na+-HCO3- co-transporter NBCn1 to the plasma membrane, centrosomes, spindle and primary cilia
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Dynamic localization of the Na+-HCO3- co-transporter NBCn1 to the plasma membrane, centrosomes, spindle and primary cilia. / Severin, Marc; Pedersen, Emma Lind; Borre, Magnus Thane; Axholm, Ida; Christiansen, Frederik Bendix; Ponniah, Muthulakshmi; Czaplinska, Dominika; Larsen, Tanja; Pardo, Luis Angel; Pedersen, Stine Falsig.
In: Journal of Cell Science, Vol. 136, No. 7, jcs260687, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dynamic localization of the Na+-HCO3- co-transporter NBCn1 to the plasma membrane, centrosomes, spindle and primary cilia
AU - Severin, Marc
AU - Pedersen, Emma Lind
AU - Borre, Magnus Thane
AU - Axholm, Ida
AU - Christiansen, Frederik Bendix
AU - Ponniah, Muthulakshmi
AU - Czaplinska, Dominika
AU - Larsen, Tanja
AU - Pardo, Luis Angel
AU - Pedersen, Stine Falsig
N1 - Publisher Copyright: © 2023. Published by The Company of Biologists Ltd.
PY - 2023
Y1 - 2023
N2 - Finely tuned regulation of transport protein localization is vital for epithelial function. The Na+-HCO3- co-transporter NBCn1 (also known as SLC4A7) is a key contributor to epithelial pH homeostasis, yet the regulation of its subcellular localization is not understood. Here, we show that a predicted N-terminal β-sheet and short C-terminal α-helical motif are essential for NBCn1 plasma membrane localization in epithelial cells. This localization was abolished by cell-cell contact disruption, and co-immunoprecipitation (co-IP) and proximity ligation (PLA) revealed NBCn1 interaction with E-cadherin and DLG1, linking it to adherens junctions and the Scribble complex. NBCn1 also interacted with RhoA and localized to lamellipodia and filopodia in migrating cells. Finally, analysis of native and GFP-tagged NBCn1 localization, subcellular fractionation, co-IP with Arl13B and CEP164, and PLA of NBCn1 and tubulin in mitotic spindles led to the surprising conclusion that NBCn1 additionally localizes to centrosomes and primary cilia in non-dividing, polarized epithelial cells, and to the spindle, centrosomes and midbodies during mitosis. We propose that NBCn1 traffics between lateral junctions, the leading edge and cell division machinery in Rab11 endosomes, adding new insight to the role of NBCn1 in cell cycle progression.
AB - Finely tuned regulation of transport protein localization is vital for epithelial function. The Na+-HCO3- co-transporter NBCn1 (also known as SLC4A7) is a key contributor to epithelial pH homeostasis, yet the regulation of its subcellular localization is not understood. Here, we show that a predicted N-terminal β-sheet and short C-terminal α-helical motif are essential for NBCn1 plasma membrane localization in epithelial cells. This localization was abolished by cell-cell contact disruption, and co-immunoprecipitation (co-IP) and proximity ligation (PLA) revealed NBCn1 interaction with E-cadherin and DLG1, linking it to adherens junctions and the Scribble complex. NBCn1 also interacted with RhoA and localized to lamellipodia and filopodia in migrating cells. Finally, analysis of native and GFP-tagged NBCn1 localization, subcellular fractionation, co-IP with Arl13B and CEP164, and PLA of NBCn1 and tubulin in mitotic spindles led to the surprising conclusion that NBCn1 additionally localizes to centrosomes and primary cilia in non-dividing, polarized epithelial cells, and to the spindle, centrosomes and midbodies during mitosis. We propose that NBCn1 traffics between lateral junctions, the leading edge and cell division machinery in Rab11 endosomes, adding new insight to the role of NBCn1 in cell cycle progression.
KW - Acid-base transport
KW - Cell polarity
KW - Cell–cell adhesion
KW - Mitosis
KW - Primary cilium
KW - Scribble complex
U2 - 10.1242/jcs.260687
DO - 10.1242/jcs.260687
M3 - Journal article
C2 - 37039101
AN - SCOPUS:85152111149
VL - 136
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 7
M1 - jcs260687
ER -
ID: 344810685