Non‐centrosomal microtubules regulate <scp>F</scp>‐actin organization through the suppression of <scp>GEF</scp>‐<scp>H</scp>1 activity

Nagae, Shigenori; Meng, Wenxiang; Takeichi, Masatoshi

doi:10.1111/gtc.12044

Cited by 37 publications

(36 citation statements)

References 32 publications

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“…These findings are consistent with increased GEF-H1 targeting to the MTs caused by PAK1 phosphorylation. Additional support for our observation came from a recent report by Nagae et al (38), who described the existence of two populations: centrosomal and non-centrosomal MTs. These MT populations were shown to have different biochemical characteristics, mechanisms of stabilization, and preference for GEF-H1 binding.…”

Section: Phosphorylation Of Sersupporting

confidence: 88%

Control of Vascular Permeability by Atrial Natriuretic Peptide via a GEF-H1-dependent Mechanism

Tian

Gawlak

et al. 2014

Journal of Biological Chemistry

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Background: Regulation of vascular permeability by microtubule (MT)-associated proteins is not well understood. Results: ANP promoted MT peripheral growth and protected endothelial barrier via Rac-PAK1-dependent inactivation of GEF-H1 and consequent suppression of Rho signaling. Conclusion: A PAK1-GEF-H1 dependent mechanism mediates endothelial barrier protection by ANP. Significance: Modulation of GEF-H1 activity represents a novel approach in prevention of pathologic vascular leak.

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Section: Phosphorylation Of Sersupporting

confidence: 88%

Control of Vascular Permeability by Atrial Natriuretic Peptide via a GEF-H1-dependent Mechanism

Tian

Gawlak

et al. 2014

Journal of Biological Chemistry

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“…CAMSAP3 (also known as Nezha) is a member of the calmodulin-regulatedspectrin-associated proteins (CAMSAP)/Nezha/Patronin family proteins, which bind and stabilize the minus-ends of microtubules (11)(12)(13)(14)(15)(16)(17)(18). In cultured mammalian cells, CAMSAP proteins have been shown to stabilize noncentrosomal microtubules in the cytoplasm or cell junctions (11,14,19,20), suggesting their possible involvement in the spatial regulation of microtubule assembly in polarized cells, such as epithelial-specific longitudinal microtubule alignment.…”

mentioning

confidence: 99%

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

Toya¹,

Kobayashi²,

Kawasaki³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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129

171

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Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated–spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells.

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“…1A) (24,26). Recent work has demonstrated that CAMSAP2 and CAMSAP3 bind MT minus-ends and that depletion of these proteins causes a reduction in MT numbers and changes the MT organization in epithelial cells (28,29). The Caenorhabditis…”

mentioning

confidence: 99%

Regulation of microtubule minus-end dynamics by CAMSAPs and Patronin

Hendershott

Vale

2014

Proc. Natl. Acad. Sci. U.S.A.

158

184

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The microtubule (MT) cytoskeleton plays an essential role in mitosis, intracellular transport, cell shape, and cell migration. The assembly and disassembly of MTs, which can occur through the addition or loss of subunits at the plus-or minus-ends of the polymer, is essential for MTs to carry out their biological functions. A variety of proteins act on MT ends to regulate their dynamics, including a recently described family of MT minus-end binding proteins called calmodulin-regulated spectrin-associated protein (CAMSAP)/Patronin/Nezha. Patronin, the single member of this family in Drosophila, was previously shown to stabilize MT minusends against depolymerization in vitro and in vivo. Here, we show that all three mammalian CAMSAP family members also bind specifically to MT minus-ends and protect them against kinesin-13-induced depolymerization. However, these proteins differ in their abilities to suppress tubulin addition at minus-ends and to dissociate from MTs. CAMSAP1 does not interfere with polymerization and tracks along growing minus-ends. CAMSAP2 and CAMSAP3 decrease the rate of tubulin incorporation and remain bound, thereby creating stretches of decorated MT minus-ends. By using truncation analysis, we find that somewhat different minimal domains of CAMSAP and Patronin are involved in minus-end localization. However, we find that, in both cases, a highly conserved C-terminal domain and a more variable central domain cooperate to suppress minus-end dynamics in vitro and that both regions are required to stabilize minus-ends in Drosophila S2 cells. These results show that members of the CAMSAP/Patronin family all localize to and protect minus-ends but have evolved distinct effects on MT dynamics.tubulin polymerization | cytoskeletal regulation | TIRF microscopy M icrotubules (MTs) are cellular polymers that are important for a variety of functions, including cargo transport and mitotic spindle formation. MTs are composed of dimers of α-and β-tubulin that assemble head-to-tail, creating a polar protofilament. Protofilaments then assemble laterally to form the canonical 13-protofilament MT structure, with β-tubulin exposed at fast-growing plus-ends and α-tubulin exposed at slow-growing minus-ends (1). MTs exhibit an intriguing property termed "dynamic instability," whereby the polymer can abruptly switch between episodes of net growth and shrinkage (2). The rates of growth and shrinkage as well as the frequency of transitions between these two states are regulated by numerous MT-associated proteins, many of which bind to the ends of the polymer (3, 4).The dynamics of MT plus-ends are regulated by a well-characterized network of plus-end tracking proteins (+TIPs) (5). End-binding proteins recognize a tubulin conformation unique to the growing ends of MTs and can affect the dynamics of plusends by intrinsically altering the structure of the MT end (6-8) as well as recruiting other interacting proteins (9). In contrast, TOG domain-containing proteins, such as XMAP215, promote MT growth and have been suggested ...

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Non‐centrosomal microtubules regulate F‐actin organization through the suppression of GEF‐H1 activity

Cited by 37 publications

References 32 publications

Control of Vascular Permeability by Atrial Natriuretic Peptide via a GEF-H1-dependent Mechanism

Control of Vascular Permeability by Atrial Natriuretic Peptide via a GEF-H1-dependent Mechanism

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

Regulation of microtubule minus-end dynamics by CAMSAPs and Patronin

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