Direct Regulation of Microtubule Dynamics by KIF17 Motor and Tail Domains

Acharya, Bipul R.; Espenel, Cédric; Kreitzer, Geri

doi:10.1074/jbc.m113.494989

Cited by 19 publications

(19 citation statements)

References 46 publications

(41 reference statements)

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“…Intracellular movement along microtubules mediated by interactions between microtubule motors, such as kinesins, and cargo is an important transport mechanism (Hirokawa, 1998;Miki et al, 2005). Kif17 regulates the dynamics and organization of microtubules by interacting with EB1 at microtubule plus ends and thereby promotes epithelial differentiation (Acharya et al, 2013). However, Kif17 tended to accumulate at the spindle pole (microtubule minus ends) in oocytes and this was controlled by Rab23, which interacted with Kif17.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Cytoskeletal dynamics are involved in multiple cellular processes during oocyte meiosis, including spindle organization, actin-based spindle migration and polar body extrusion. Here, we report that the vesicle trafficking protein Rab23, a GTPase, drives the motor protein Kif17, and that this is important for spindle organization and actin dynamics during mouse oocyte meiosis. GTP-bound Rab23 accumulated at the spindle and promoted migration of Kif17 to the spindle poles. Depletion of Rab23 or Kif17 caused polar body extrusion failure. Further analysis showed that depletion of Rab23/ Kif17 perturbed spindle formation and chromosome alignment, possibly by affecting tubulin acetylation. Kif17 regulated tubulin acetylation by associating with αTAT and Sirt2, and depletion of Kif17 altered expression of these proteins. Moreover, depletion of Kif17 decreased the level of cytoplasmic actin, which abrogated spindle migration to the cortex. The tail domain of Kif17 associated with constituents of the RhoA-ROCK-LIMK-cofilin pathway to modulate assembly of actin filaments. Taken together, our results demonstrate that the Rab23-Kif17-cargo complex regulates tubulin acetylation for spindle organization and drives actin-mediated spindle migration during meiosis.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…When KIF17 is depleted from these cells, they fail to form a single lumen and apical markers GP135 and GP114 remain randomly localized on the plasma membrane. KIF17 depletion and overexpression experiments in 2D cultures revealed that KIF17 attenuates MT dynamics, stabilizes MTs, induces cortical MTand actin remodeling by activating RhoA locally, and stabilizes E-cadherin at AJ (Acharya et al 2013(Acharya et al , 2016Jaulin and Kreitzer 2010). Despite the similar failure of KIF3A-and KIF17-depleted cells to position apical membrane markers and form apical lumens, differences in how these kinesins affect MTs suggest they do not act by entirely equivalent mechanisms.…”

Section: Microtubule Motor Proteins and Lumen Formationmentioning

confidence: 99%

“…In contrast, a truncated, constitutively active kinesin-1 accumulates in the neurite that becomes an axon and may play a role in axon specification (Jacobson et al 2006). In cultured epithelial cells, kinesin-2 family motors KIF3A/B and KIF17 contribute to regulation of MT dynamics and stabilization, to cytoskeletal remodeling, and to positioning sites of apical membrane insertion and lumen formation (Jaulin and Kreitzer 2010;Acharya et al 2013Acharya et al , 2016Boehlke et al 2013;Li et al 2014a). Both motors localize to MT plus ends and regulate MT plusend dynamics, but appear to affect epithelial polarity by distinct mechanisms, as highlighted below.…”

Section: Microtubule Motors In Initiation Of Epithelial Polarizationmentioning

confidence: 99%

“…The localization of KIF17 at MT plus ends depends on EB1, which activates KIF17 by relieving its autoinhibited conformation (Espenel et al 2013). In vitro, EB1 enhances the binding and ATPase activity of KIF17, but is not required to stabilize MTs (Acharya et al 2013). Importantly, unlike KIF4-mediated MTstabilization in fibroblasts, KIF17, at least in part, appears to act upstream of RhoA in epithelial cells (Acharya et al 2016).…”

Section: Coordinating Cytoskeletal Remodeling With Remodeling Of Cellmentioning

confidence: 99%

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Microtubule Motors in Establishment of Epithelial Cell Polarity

Kreitzer

Myat

2017

Cold Spring Harb Perspect Biol

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Epithelial cells play a key role in insuring physiological homeostasis by acting as a barrier between the outside environment and internal organs. They are also responsible for the vectorial transport of ions and fluid essential to the function of many organs. To accomplish these tasks, epithelial cells must generate an asymmetrically organized plasma membrane comprised of structurally and functionally distinct apical and basolateral membranes. Adherent and occluding junctions, respectively, anchor cells within a layer and prevent lateral diffusion of proteins in the outer leaflet of the plasma membrane and restrict passage of proteins and solutes through intercellular spaces. At a fundamental level, the establishment and maintenance of epithelial polarity requires that signals initiated at cell-substratum and cell-cell adhesions are transmitted appropriately and dynamically to the cytoskeleton, to the membrane-trafficking machinery, and to the regulation of occluding and adherent junctions. Rigorous descriptive and mechanistic studies published over the last 50 years have provided great detail to our understanding of epithelial polarization. Yet still, critical early steps in morphogenesis are not yet fully appreciated. In this review, we discuss how cytoskeletal motor proteins, primarily kinesins, contribute to coordinated modification of microtubule and actin arrays, formation and remodeling of cell adhesions to targeted membrane trafficking, and to initiating the formation and expansion of an apical lumen.

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“…KIF17 constructs used for this study were amplified by PCR from human A549 or Caco2 cells and cloned into Gateway expression vectors (Invitrogen) as recommended by the manufacturer and as described previously (Jaulin and Kreitzer, 2010;Acharya et al, 2013). Myc-C3, GFP-RhoA WT, myc-RhoA V14 , and myc-RhoA N19 were generous gifts from Dr Alan Hall (Memorial Sloan Kettering Cancer Center, NY, USA).…”

Section: Expression Constructsmentioning

confidence: 99%

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

Acharya

Espenel

Libanje

et al. 2016

Journal of Cell Science

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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.

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Direct Regulation of Microtubule Dynamics by KIF17 Motor and Tail Domains

Cited by 19 publications

References 46 publications

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

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

Microtubule Motors in Establishment of Epithelial Cell Polarity

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

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