Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells.

Abstract:

: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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Linford A,Yoshimura S,Nunes Bastos R,Langemeyer L,Gerondopoulos A,Rigden DJ,Barr FA

doi

10.1016/j.devcel.2012.04.010

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

952-66

issue

5

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(12)00187-6

journal_volume

22

pub_type

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