KIF17 regulates RhoA-dependent actin remodeling at epithelial cell–cell adhesions

Abstract

The kinesin KIF17 localizes at microtubule plus-ends where it contributes to regulation of microtubule stabilization and epithelial polarization. We now show that KIF17 localizes at cell-cell adhesions and that KIF17 depletion inhibits accumulation of actin at the apical pole of cells grown in 3D organotypic cultures and alters the distribution of actin and E-cadherin in cells cultured in 2D on solid supports. Overexpression of full-length KIF17 constructs or truncation mutants containing the N-terminal motor domain resulted in accumulation of newly incorporated GFP-actin into junctional actin foci, cleared E-cadherin from cytoplasmic vesicles and stabilized cell-cell adhesions to challenge with calcium depletion. Expression of these KIF17 constructs also increased cellular levels of active RhoA, whereas active RhoA was diminished in KIF17-depleted cells. Inhibition of RhoA or its effector ROCK, or expression of LIMK1 kinase-dead or activated cofilin S3A inhibited KIF17-induced junctional actin accumulation. Interestingly, KIF17 activity toward actin depends on the motor domain but is independent of microtubule binding. Together, these data show that KIF17 can modify RhoA-GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells.

Rab23/Kif17 regulate meiotic progression in oocytes by modulating tubulin acetylation and actin dynamics

“…Further analysis indicated that regulators of actin assembly, such as RhoA, ROCK1, p-LIMK and p-cofilin, were downregulated in Kif17-KD oocytes. Kif17 regulates RhoA-dependent actin remodeling in epithelial cell-cell adhesions (Acharya et al, 2016). However, our co-immunoprecipitation results showed that components of the RhoA pathway bound to the tail domain of Kif17, suggesting that Kif17 forms a platform for these molecules.…”

“…Septin 9 directly associates with the tail domain of Kif17 and modulates the interactions of this motor protein with membrane cargo (Bai et al, 2016;Wong-Riley and Besharse, 2012). Furthermore, Kif17 reportedly regulates RhoA-dependent actin remodeling at epithelial cell-cell adhesions (Acharya et al, 2016).…”

The role of microtubules in the regulation of epithelial junctions

“…51 In agreement, the KO of KAP3, a subunit of kinesin-2, results in decreased levels of N-cadherin and β-catenin in embryonic mouse neural precursors, 52 whereas the overexpression of another kinesin, KIF17, promotes the apical and junctional accumulation of actin and E-cadherin, respectively. 53 In epithelial Pkt2 cells cytoplasmic dynein transiently tethers MTs at sites of cell-cell contact during junction biogenesis, providing a track for the kinesin-dependent delivery of junctional components. 54 Another plus-end binding protein, CLIP170, targets MTs to AJs prior to apico-basal array assembly.…”

Signaling by Small GTPases at Cell–Cell Junctions: Protein Interactions Building Control and Networks

“…KIF17 is a microtubule motor that interacts with the plus-end microtubule capture machinery at the cell cortex. Expression of KIF17 increases active RhoA and junctional actin levels, thereby stabilizing cellcell contacts (Acharya et al 2016). Although the GEF responsible for these effects is not known, these results suggest that modification of microtubule dynamics in more subtle ways also have an impact on RhoA signaling.…”