RAB6 and microtubules restrict secretion to focal adhesions

Fourrière, Lou; Kasri, Amal; Gareil, Nelly; Bardin, Sabine; Boulanger, Jérôme; Sikora, Romain; Boncompain, Gaëlle; Miserey-Lenkei, Stéphanie; Perez, Franck; Goud, Bruno

doi:10.1101/382176

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…The targeting of focal adhesions by microtubules have been shown to control focal adhesion dynamics through vesicular traffic (Ezratty et al, 2009, Ezratty et al, 2005, Shafaq-Zadah et al, 2016, suggesting that microtubule acetylation effect on focal adhesion dynamics may involve the regulation vesicular traffic. The small GTPase Rab6 decorates most post-Golgi carriers (Fourriere et al, 2018). Moreover Rab6 and Rab8 have been involved in vesicular traffic to and from focal adhesions (Stehbens et al, 2014, Grigoriev et al, 2007.…”

Section: αTat1 Controls Rab6 Vesicle Fusion At Focal Adhesionsmentioning

confidence: 99%

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

Bance

Seetharaman

Leduc

et al. 2018

Preprint

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140 w) Microtubules play a crucial role in mesenchymal migration by controlling cell polarity and the turnover of cell adhesive structures on the extracellular matrix. The polarized functions of microtubules imply that microtubules are locally regulated. Here, we investigated the regulation and role of two major tubulin post-translational modifications, acetylation and detyrosination, which have been associated with stable microtubules. Using primary astrocytes in a wound healing assay, we show that these tubulin modifications are independently regulated during cell polarization and differently affect cell migration. In contrast to microtubule detyrosination, αTAT1-mediated microtubule acetylation increases in the vicinity of focal adhesions and promotes cell migration. We further demonstrate that αTAT1 increases focal adhesion turnover by promoting Rab6positive vesicle fusion at focal adhesions. Our results highlight the specificity of microtubule post-translational modifications and bring new insight into the regulatory functions of tubulin acetylation.

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Section: αTat1 Controls Rab6 Vesicle Fusion At Focal Adhesionsmentioning

confidence: 99%

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

Bance

Seetharaman

Leduc

et al. 2018

Preprint

View full text Add to dashboard Cite

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The exocyst complex is an essential component of the mammalian constitutive secretory pathway

Pereira

Stalder

Anderson

et al. 2022

Preprint

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Secreted proteins fulfil a vast array of different functions, including adaptive immunity, cell signalling and extracellular matrix remodelling. In the trans-Golgi network, proteins destined for constitutive secretion are sorted into post-Golgi carriers which fuse with the plasma membrane to deliver their contents to the extracellular space. The molecular machinery involved is poorly understood. Here, we have used kinetic trafficking assays and transient CRISPR knock-outs to study the biosynthetic sorting route from the Golgi apparatus to the plasma membrane. Depletion of core-exocyst subunits reduces carrier fusion and causes cargo accumulation in the post-Golgi carriers. Exocyst subunits co-localise with carriers fusing at the plasma membrane and we show that the exocyst complex is recruited directly to these carriers. Abrogation of exocyst followed by kinetic trafficking assays with multiple different soluble cargoes results in cargo accumulation of all tested cargoes. Unbiased secretomics reveals a drastic reduction in the secretion of soluble proteins to the extracellular milieu after knock-out of exocyst subunits. Importantly, the knock-out of exocyst subunits in specialised secretory cell types prevents the constitutive secretion of antibodies in lymphocytes and of the hormones leptin and adiponectin in adipocytes. Together these data identify the exocyst complex as the functional tether of secretory post-Golgi carriers at the plasma membrane and an essential component of the mammalian constitutive secretory pathway.

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Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and astrocyte migration

Bance

Seetharaman

Leduc

et al. 2019

Journal of Cell Science

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Microtubules play a crucial role in mesenchymal migration by controlling cell polarity and the turnover of cell adhesive structures on the extracellular matrix. The polarized functions of microtubules imply that microtubules are locally regulated. Here, we investigated the regulation and role of two major tubulin post-translational modifications, acetylation and detyrosination, which have been associated with stable microtubules. Using primary astrocytes in a wound healing assay, we show that these tubulin modifications are independently regulated during cell polarization and differently affect cell migration. In contrast to microtubule detyrosination, αTAT1 (ATAT1)-mediated microtubule acetylation increases in the vicinity of focal adhesions and promotes cell migration. We further demonstrate that αTAT1 increases focal adhesion turnover by promoting Rab6-positive vesicle fusion at focal adhesions. Our results highlight the specificity of microtubule posttranslational modifications and bring new insight into the regulatory functions of tubulin acetylation. This article has an associated First Person interview with the first author of the paper.

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RAB6 and microtubules restrict secretion to focal adhesions

Cited by 4 publications

References 37 publications

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

The exocyst complex is an essential component of the mammalian constitutive secretory pathway

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and astrocyte migration

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