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

• DOI: 10.1242/jcs.226886
• Publication Date: 2019-04-11T13:35:43Z
• Authors: Aurélien Bidaud-M...; Florian Bossard; Andrea Schnúr; Ryosuke Fukuda; Guido Veit; Haijin Xu; Gergely L. Lukacs
• Keywords: Transcytosis; Polarity (international relations); Cell polarity

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