Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals—Illustrated with Four Actin Cytoskeleton Proteins

Akram, Zain; Ahmed, Ishtiaq; Mack, Heike Heike; Kaur, Romandeep; Silva, Richard; Castilho, Beatriz A.; Friant, Sylvie; Sattlegger, Evelyn; Munn, Alan Leslie

doi:10.3390/cells9030672

Cited by 12 publications

(5 citation statements)

References 286 publications

(898 reference statements)

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“…We do not observe density for actin, present in vertebrate γTuRC [10][11][12] , in the lumen of the S. cerevisiae γTuRC. This is consistent with actin not being present in the S. cerevisiae nucleus 39 .…”

Section: Coiled-coil Proteins Stabilize the Rst Row Of α/β-Tubulinsupporting

confidence: 87%

Structure of the native γ-Tubulin Ring Complex capping spindle microtubules

Barford,

Dendooven,

Yatskevich

et al. 2023

Preprint

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Microtubules (MTs) are fundamental to cellular architecture, function and organismal development1. MT filaments assemble the mitotic spindle apparatus responsible for chromosome segregation, whereas the MT-based cytoskeletal network mediates dynein and kinesin-based intracellular transport. MTs are formed by the dynamic oligomerization and depolymerization of α/β-tubulin dimers in a head-to-tail fashion, with α-tubulin exposed at the ‘minus’ end of MTs and β-tubulin capping the more dynamic MT ‘plus’ end2. In cells, the large and evolutionary conserved γ-Tubulin Ring Complex (γTuRC) templates efficient MT nucleation from their ‘minus’ end at MT-organizing centres (MTOCs)3–6. Because all known γTuRC structures are devoid of MTs and exhibit an ‘open’, inactive conformation, the molecular mechanism of γTuRC-mediated MT nucleation remains unknown. Here, we used cryo-electron tomography (cryo-ET) to determine the structure of the native γTuRC capping the minus end of a MT in the context of enriched yeast mitotic spindles. In our structure, γTuRC adopts an active closed conformation to function as a perfect geometric helical template presenting a ring of g-tubulin subunits to seed nucleation of exclusively 13-protofilament microtubules. Our cryo-ET reconstruction also revealed that a novel coiled-coil protein staples the first row of α/β-tubulin molecules directly to alternating positions along the γ-tubulin ring. This positioning of α/β-tubulin onto γTuRC reveals a role for the coiled-coil protein in augmenting γTuRC-mediated microtubule nucleation. Based on our results we describe a molecular model for γTuRC activation and MT nucleation.

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Section: Coiled-coil Proteins Stabilize the Rst Row Of α/β-Tubulinsupporting

confidence: 87%

Structure of the native γ-Tubulin Ring Complex capping spindle microtubules

Barford,

Dendooven,

Yatskevich

et al. 2023

Preprint

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“…These proteins exist in two isoforms: PSTPIP1 and ‐2. PSTPIP1 contains a typical F‐BAR domain in the N‐terminal part, a PEST sequence (enriched in proline [P], glutamic acid [E], serine [S] and threonine [T]) and a C‐terminal SH3 domain 27,28 . Compared with PSTPIP1, PSTPIP2 (also called MAYP for Macrophage actin‐associated tyrosine phosphorylated protein) lacks the SH3 domain 29,30 and is not able to interact with WASP (Wiskott Aldrich syndrome protein), an actin cytoskeleton regulator 31 .…”

Section: Introductionmentioning

confidence: 99%

“…[S] and threonine [T]) and a C-terminal SH3 domain. 27,28 Compared with PSTPIP1, PSTPIP2 (also called MAYP for Macrophage actinassociated tyrosine phosphorylated protein) lacks the SH3 domain 29,30 and is not able to interact with WASP (Wiskott Aldrich syndrome protein), an actin cytoskeleton regulator. 31 Both PSTPIP proteins regulate filopodia formation in macrophages and F-actin cytoskeleton, and their mutated versions lead to autoinflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

N‐BAR and F‐BAR proteins—endophilin‐A3 and PSTPIP1—control clathrin‐independent endocytosis of L1CAM

Lemaigre

Ceuppens

Valades-Cruz

et al. 2023

Traffic

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Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrinmediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM

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“…EEF1A1 binds actin and modulates the cytoskeleton organization responsible for cell migration [ 38 , 39 ]. Thus, it is plausible that the migratory ability of osteosarcoma, chondrosarcoma, and antler cartilage cells markedly declined with the inhibition of EEF1A1.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1

Yang

Ming

et al. 2023

IJMS

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MicroRNAs (miRNAs) play a crucial role in maintaining the balance between the rapid growth and suppression of tumorigenesis during antler regeneration. This study investigated the role of a novel miRNA, PC-3p-2869 (miR-PC-2869), in antler growth and its therapeutic potential in human osteosarcoma and chondrosarcoma. Stem-loop RT-qPCR showed that miR-PC-2869 was expressed extensively in diverse layers of antler tissues. Overexpression of miR-PC-2869 suppressed the proliferation and migration of antler cartilage cells. Similarly, heterologous expression of miR-PC-2869 reduced the proliferation, colony formation, and migration of osteosarcoma cell line MG63 and U2OS and chondrosarcoma cell line SW1353. Moreover, 18 functional target genes of miR-PC-2869 in humans were identified based on the screening of the reporter library. Among them, 15 target genes, including CDK8, EEF1A1, and NTN1, possess conserved miR-PC-2869-binding sites between humans and red deer (Cervus elaphus). In line with this, miR-PC-2869 overexpression decreased the expression levels of CDK8, EEF1A1, and NTN1 in MG63, SW1353, and antler cartilage cells. As expected, the knockdown of CDK8, EEF1A1, or NTN1 inhibited the proliferation and migration of MG63, SW1353, and antler cartilage cells, demonstrating similar suppressive effects as miR-PC-2869 overexpression. Furthermore, we observed that CDK8, EEF1A1, and NTN1 mediated the regulation of c-myc and cyclin D1 by miR-PC-2869 in MG63, SW1353, and antler cartilage cells. Overall, our work uncovered the cellular functions and underlying molecular mechanism of antler-derived miR-PC-2869, highlighting its potential as a therapeutic candidate for bone cancer.

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Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals—Illustrated with Four Actin Cytoskeleton Proteins

Cited by 12 publications

References 286 publications

Structure of the native γ-Tubulin Ring Complex capping spindle microtubules

Structure of the native γ-Tubulin Ring Complex capping spindle microtubules

N‐BAR and F‐BAR proteins—endophilin‐A3 and PSTPIP1—control clathrin‐independent endocytosis of L1CAM

MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1

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