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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 (\u223c35%) and endocytic (\u223c65%) 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\u2013CFTR 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.<\/jats:p>","DOI":"10.1242\/jcs.226886","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T09:35:43Z","timestamp":1554975343000},"source":"Crossref","is-referenced-by-count":12,"title":["Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting"],"prefix":"10.1242","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-3827","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Bidaud-Meynard","sequence":"first","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Bossard","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schn\u00far","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Fukuda","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Veit","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijin","family":"Xu","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0675","authenticated-orcid":false,"given":"Gergely L.","family":"Lukacs","sequence":"additional","affiliation":[{"name":"McGill University 1 Department of Physiology , , Montr\u00e9al, QC, H3G 1Y6 , Canada"},{"name":"McGill University 2 Department of Biochemistry , , Montr\u00e9al, QC, H3G 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"2024061318131480900_JCS226886C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jcf.2006.09.002","article-title":"Endocytic trafficking of CFTR in health and disease","volume":"6","author":"Ameen","year":"2007","journal-title":"J. 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