TY - JOUR
T1 - Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions
AU - Bouchet, Benjamin P
AU - Gough, Rosemarie E
AU - Ammon, York-Christoph
AU - van de Willige, Dieudonnée
AU - Post, Harm
AU - Jacquemet, Guillaume
AU - Altelaar, Af Maarten
AU - Heck, Albert Jr
AU - Goult, Benjamin T
AU - Akhmanova, Anna
PY - 2016/7/13
Y1 - 2016/7/13
N2 - The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5β and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules.
AB - The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5β and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules.
KW - Adaptor Proteins, Signal Transducing
KW - Cytoskeletal Proteins
KW - Focal Adhesions/metabolism
KW - HEK293 Cells
KW - HeLa Cells
KW - Humans
KW - Microtubules/metabolism
KW - Talin/metabolism
KW - Tumor Suppressor Proteins/metabolism
U2 - 10.7554/eLife.18124
DO - 10.7554/eLife.18124
M3 - Article
C2 - 27410476
SN - 2050-084X
VL - 5
JO - Elife
JF - Elife
M1 - e18124
ER -