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Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions.

Original publication

DOI

10.1016/j.devcel.2012.04.010

Type

Journal article

Journal

Dev Cell

Publication Date

15/05/2012

Volume

22

Pages

952 - 966

Keywords

ADAM Proteins, ADAM10 Protein, Adherens Junctions, Amyloid Precursor Protein Secretases, Biological Transport, Cadherins, Cell Movement, Endosomes, Epithelial Cells, Guanine Nucleotide Exchange Factors, HEK293 Cells, HeLa Cells, Humans, Membrane Proteins, Protein Transport, Transferrin, Vesicular Transport Proteins, rab GTP-Binding Proteins, rab4 GTP-Binding Proteins