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Abstract
Apical lumen formation is a key step during epithelial morphogenesis of tubular organs. Appropriate transport and targeting of apical proteins to the apical membrane initiation site (AMIS) plays a crucial role in establishing a solitary, central lumen. FIP5, a Rab11-interacting protein, is an important regulator that directs apical endosome trafficking along microtubules toward the AMIS during cytokinesis. However, it is unknown which molecular motor(s) transports FIP5-positive apical endosomes during lumen initiation, and how this process is regulated. In this study, we demonstrate that the interaction of FIP5 with the microtubule motor, Kinesin-2, is required for the movement of FIP5-endosomes and delivery of these endosomes from centrosomes to the cleavage furrow during apical lumen initiation. Loss of Kinesin-2 disrupts targeting of apical proteins to the AMIS and results in multiple lumen formation in MDCK cysts. Our data provide more details to the molecular mechanism of FIP5-dependent apical trafficking during apical lumen formation.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Irene Choi for critical reading of the manuscript. We are appreciative of Dr. Charles Yeaman (University of Iowa) for anti-gp135 antibody. We also thank Dr. Cedric Delevoye (Institut Curie) for providing GFP-Kif13A-tail construct. This work was supported by a grant from the NIH-NIDDK (DK064380 to RP).
Supplementary Material
Supplementary material may be downloaded here: www.landesbioscience.com/journals/cellularlogistics/article/28928/