title: The kinesin KIF16B mediates apical transcytosis of transferrin receptor in AP-1B-deficient epithelia.
abstract: Polarized epithelial cells take up nutrients from the blood through receptors that are endocytosed and recycle back to the basolateral plasma membrane (PM) utilizing the epithelial-specific clathrin adaptor AP-1B. Some native epithelia lack AP-1B and therefore recycle cognate basolateral receptors to the apical PM, where they carry out important functions for the host organ. Here, we report a novel transcytotic pathway employed by AP-1B-deficient epithelia to relocate AP-1B cargo, such as transferrin receptor (TfR), to the apical PM. Lack of AP-1B inhibited basolateral recycling of TfR from common recycling endosomes (CRE), the site of function of AP-1B, and promoted its transfer to apical recycling endosomes (ARE) mediated by the plus-end kinesin KIF16B and non-centrosomal microtubules, and its delivery to the apical membrane mediated by the small GTPase rab11a. Hence, our experiments suggest that the apical recycling pathway of epithelial cells is functionally equivalent to the rab11a-dependent TfR recycling pathway of non-polarized cells. They define a transcytotic pathway important for the physiology of native AP-1B-deficient epithelia and report the first microtubule motor involved in transcytosis.
authors.affiliation: Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Andres E
authors.initials: AE
authors.lastname: Perez Bay
authors.forename: Ryan
authors.initials: R
authors.lastname: Schreiner
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzoni
authors.forename: Jose M
authors.initials: JM
authors.lastname: Carvajal-Gonzalez
authors.forename: Diego
authors.initials: D
authors.lastname: Gravotta
authors.forename: Emilie
authors.initials: E
authors.lastname: Perret
authors.forename: Gullermo
authors.initials: G
authors.lastname: Lehmann Mantaras
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Rodriguez-Boulan
mesh_terms: D033961:Adaptor Protein Complex 1; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D057900:Transcytosis; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D033961:Adaptor Protein Complex 1; D016547:Kinesins; D011990:Receptors, Transferrin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C504670:KIF16B protein, human