Rab21 (green) brings β1 integrins into vesicles.

Proper trafficking of integrins is important for cell adhesion and migration, but the machinery involved has been unknown. On page 767, Pellinen et al. report that small GTPase Rab proteins that are known to be important for endocytosis and exocytosis associate with integrins and facilitate their internalization and recycling.

In epithelial cancer cells, β1-containing integrin heterodimers associated with Rab21. Rab21 expression triggered localization of active β1 integrin and Rab21 to large vesicles, consistent with Rab21 being an early endosomal protein. A large fraction of the integrin rapidly returned to the cell surface.

Cells that overexpressed Rab21 attached to the substrate more efficiently than did wild-type cells, whereas cells treated with Rab21 siRNAs had less affinity for the substrate and migrated less efficiently in a wounding assay.

As Rab 21 did not alter the amount of integrins in the cell, the team hypothesizes that it affects attachment and migration by increasing integrin recycling to newly formed sites of attachment. The researchers hypothesize that the integrins are stripped of their ligands in the vesicle and thus readied to return to the surface to bind new substrate.