The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

Girdler, Gemma; Applewhite, Derek A.; Perry, Wick M. G.; Rogers, Stephen L.; Röper, Katja

doi:10.1242/dev.134445

Cited by 4 publications

(13 citation statements)

References 32 publications

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“…At very high expression levels, both the GAR domain and the unstructured C-terminus could bind to and bundle MTs, and the same was true for the complete Tail fragment ( Fig EV3). Our results match those reported for comparable truncation mutants of the Drosophila Gas2L ortholog Pigs [19]. Mutating the SxIP motif to SxAA, and therefore abolishing the binding of the Tail fragment to EB proteins and MT plus ends, did not significantly alter the binding of the Tail to MT shafts.…”

Section: Autoinhibition Of Gas2l1 Is a Results Of The Interaction Betwsupporting

confidence: 89%

“…Our results complement previous observations hinting towards an inhibitory relation between the CH and GAR domains of Gas2L proteins in other cell types [16,19]. We propose that this property depends on the autoinhibition of Gas2L1.…”

Section: Discussionsupporting

confidence: 91%

“…This is in line with other studies investigating Gas2L proteins [16,19,21]. Together with the dramatic changes induced by Gas2L1 overexpression, these findings suggest that the protein is extremely potent and that endogenous expression levels of Gas2L1 are low.…”

Section: Discussionsupporting

confidence: 91%

“…Evidence for the binding selectivity of Gas2L1 was already provided by previous studies [18,19]. Purified Gas2L1 does not associate with individual actin filaments in vitro unless MTs are present, yet overexpressed Gas2L1 localizes to neuronal F-actin including the areas where MTs are excluded.…”

Section: Discussionmentioning

confidence: 73%

“…Like ACF7, Gas2L1 contains an N-terminal actin-binding calponin homology (CH) domain, a MT lattice-binding Gas2-related (GAR) domain and a C-terminal SxIP motif, which mediates the interaction with MT plus ends via EB proteins [16][17][18]. The actin-MT crosslinking abilities of Gas2L1 and its Drosophila ortholog Pigs (Pickled eggs) have been previously demonstrated in cells [18,19]. So far, Gas2L1 was shown to regulate the distance between centrioles in cycling cells [20], and Pigs was identified as a cytoskeletal target of Notch signalling, which participates in Drosophila wing muscle development and oogenesis [21].…”

Section: Introductionmentioning

confidence: 99%

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Cytolinker Gas2L1 regulates axon morphology through microtubule‐modulated actin stabilization

et al. 2019

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Crosstalk between the actin and microtubule cytoskeletons underlies cellular morphogenesis. Interactions between actin filaments and microtubules are particularly important for establishing the complex polarized morphology of neurons. Here, we characterized the neuronal function of growth arrest‐specific 2‐like 1 (Gas2L1), a protein that can directly bind to actin, microtubules and microtubule plus‐end‐tracking end binding proteins. We found that Gas2L1 promotes axon branching, but restricts axon elongation in cultured rat hippocampal neurons. Using pull‐down experiments and in vitro reconstitution assays, in which purified Gas2L1 was combined with actin and dynamic microtubules, we demonstrated that Gas2L1 is autoinhibited. This autoinhibition is relieved by simultaneous binding to actin filaments and microtubules. In neurons, Gas2L1 primarily localizes to the actin cytoskeleton and functions as an actin stabilizer. The microtubule‐binding tail region of Gas2L1 directs its actin‐stabilizing activity towards the axon. We propose that Gas2L1 acts as an actin regulator, the function of which is spatially modulated by microtubules.

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Section: Autoinhibition Of Gas2l1 Is a Results Of The Interaction Betwsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Cytolinker Gas2L1 regulates axon morphology through microtubule‐modulated actin stabilization

et al. 2019

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Cytoskeletal Crosstalk in Cell Migration

Seetharaman

Etienne-Manneville

2020

Trends in Cell Biology

316

231

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Cell migration is a highly dynamic process driven by the cytoskeleton, which mainly comprises the actin microfilaments, microtubules and intermediate filaments. During migration, cells polarize and form protrusions at the front where new adhesions are formed. These nascent adhesions mature into focal adhesions that transmit the traction forces required for movement.All of these steps are coupled to major cytoskeletal rearrangements and are controlled by a wide array of signaling cascades. The constant crosstalk between actin, microtubules, and intermediate filaments ensures their coordinated dynamics to facilitate cell migration. Here, we first describe how master regulators, such as RhoGTPases, can simultaneously control the three cytoskeletal structures. We then summarize the recent crosstalk mechanisms by which cytoskeletal networks can locally regulate one another in order to function in a coordinated and efficient manner during migration.

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Microtubules stabilize intercellular contractile force transmission during tissue folding

Tserunyan

Martin

2019

Preprint

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1During development, forces transmitted between cells are critical for sculpting epithelial 2 tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change 3 cell shape (e.g., apical constriction), but can also result in force transmission between 4 cells via attachments to adherens junctions. How actomyosin networks maintain 5 attachments to adherens junctions under tension is poorly understood. Here, we 6 discovered that microtubules promote actomyosin intercellular attachments in epithelia 7during Drosophila mesoderm invagination. First, we used live imaging to show a novel 8 arrangement of the microtubule cytoskeleton during apical constriction: medioapical 9Patronin (CAMSAP) foci formed by actomyosin contraction organized an apical non-10 centrosomal microtubule network. Microtubules were required for mesoderm 11 invagination but were not necessary for initiating apical contractility or adherens junction 12 assembly. Instead, microtubules promoted connections between medioapical 13 actomyosin and adherens junctions. These results delineate a role for coordination 14

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The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation

Cited by 4 publications

References 32 publications

Cytolinker Gas2L1 regulates axon morphology through microtubule‐modulated actin stabilization

Cytolinker Gas2L1 regulates axon morphology through microtubule‐modulated actin stabilization

Cytoskeletal Crosstalk in Cell Migration

Microtubules stabilize intercellular contractile force transmission during tissue folding

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