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The microtubule regulator EFA-6 forms spatially restricted cortical foci dependent on its intrinsically disordered region and interactions with tubulins.
Sandhu, Anjali; Lyu, Xiaohui; Wan, Xinghaoyun; Meng, Xuefeng; Tang, Ngang Heok; Gonzalez, Gilberto; Syed, Ishana N; Chen, Lizhen; Jin, Yishi; Chisholm, Andrew D.
Afiliación
  • Sandhu A; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Lyu X; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Wan X; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Meng X; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Tang NH; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Gonzalez G; Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Syed IN; Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Chen L; Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Jin Y; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
  • Chisholm AD; Department of Neurobiology, School of Biological Sciences, University of California San Diego, CA 92093 USA.
bioRxiv ; 2024 Apr 14.
Article en En | MEDLINE | ID: mdl-38645057
ABSTRACT
Microtubules (MTs) are dynamic components of the cytoskeleton and play essential roles in morphogenesis and maintenance of tissue and cell integrity. Despite recent advances in understanding MT ultrastructure, organization, and growth control, how cells regulate MT organization at the cell cortex remains poorly understood. The EFA-6/EFA6 proteins are recently identified membrane-associated proteins that inhibit cortical MT dynamics. Here, combining visualization of endogenously tagged C. elegans EFA-6 with genetic screening, we uncovered tubulin-dependent regulation of EFA-6 patterning. In the mature epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR). We further show the EFA-6 IDR is sufficient to form biomolecular condensates in vitro. In screens for mutants with altered GFPEFA-6 localization, we identified a novel gain-of-function (gf) mutation in an α-tubulin tba-1 that induces ectopic EFA-6 foci in multiple cell types. tba-1(gf) animals exhibit temperature-sensitive embryonic lethality, which is partially suppressed by efa-6(lf), indicating the interaction between tubulins and EFA-6 is important for normal development. TBA-1(gf) shows reduced incorporation into filamentous MTs but has otherwise mild effects on cellular MT organization. The ability of TBA-1(gf) to trigger ectopic EFA-6 foci formation requires ß-tubulin TBB-2 and the chaperon EVL-20/Arl2. The tba-1(gf)-induced EFA-6 foci display slower turnover, contain the MT-associated protein TAC-1/TACC, and require the EFA-6 MTED. Our results reveal a novel crosstalk between cellular tubulins and cortical MT regulators in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article
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