Functional analysis of the threonine motif in the β1 integrin cytoplasmic tail in mice

Integrins are ubiquitously expressed adhesion receptors with
important functions in cellular adhesion, proliferation, migration
and signaling. These functions are determined by integrin
trafficking through endosomal compartments and receptor affinity
regulation. In this thesis, we identified the distal NxxY motif of
the β1 integrin cytoplasmic tail as a molecular switch modulating a
spatiotemporally controlled binding of two FERM-domain proteins in
different cellular compartments. Kindlins mediate integrin
activation at the plasma membrane and they dislodge upon
internalization. In the endosomal compartment, the free cytoplasmic
domain is subsequently bound by sorting nexin 17 (SNX17) to inhibit
integrin degradation. We identified SNX17 as a new β1 integrin
adaptor protein, which uses the kindlin-binding site in endosomal
compartments to stabilize integrins and to promote their recycling
back to the plasma membrane.