Skip to Main content Skip to Navigation
Journal articles

Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting

Abstract : Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia and can be impaired in human diseases. Maintenance of apical polarity in the face of CFTR non-polarized delivery and inefficient apical retention of mutant CFTRs lacking PDZ-domain protein (NHERF1, also known as SLC9A3R1) interaction, remains enigmatic. Here, we show that basolateral CFTR delivery originates from biosynthetic (∼35%) and endocytic (∼65%) recycling missorting. Basolateral channels are retrieved via basolateral-to-apical transcytosis (hereafter denoted apical transcytosis), enhancing CFTR apical expression by two-fold and suppressing its degradation. In airway epithelia, CFTR transcytosis is microtubule-dependent but independent of Myo5B, Rab11 proteins and NHERF1 binding to its C-terminal DTRL motif. Increased basolateral delivery due to compromised apical recycling and accelerated internalization upon impaired NHERF1–CFTR association is largely counterbalanced by efficient CFTR basolateral internalization and apical transcytosis. Thus, transcytosis represents a previously unrecognized, but indispensable, mechanism for maintaining CFTR apical polarity that acts by attenuating its constitutive and mutation-induced basolateral missorting. © 2019. Published by The Company of Biologists Ltd.
Document type :
Journal articles
Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-02161195
Contributor : Laurent Jonchère <>
Submitted on : Thursday, June 20, 2019 - 3:10:58 PM
Last modification on : Thursday, June 18, 2020 - 12:32:06 PM

Links full text

Identifiers

Citation

A. Bidaud-Meynard, F. Bossard, A. Schnúr, R. Fukuda, G. Veit, et al.. Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting. Journal of Cell Science, Company of Biologists, 2019, 132 (10), pp.jcs226886. ⟨10.1242/jcs.226886⟩. ⟨hal-02161195⟩

Share

Metrics

Record views

36