The microtubule regulator EFA-6 forms cortical foci dependent on its intrinsically disordered region and interactions with tubulins
Anjali Sandhu,
Xiaohui Lyu,
Xinghaoyun Wan,
Xuefeng Meng,
Ngang Heok Tang,
Gilberto Gonzalez,
Ishana N. Syed,
Lizhen Chen,
Yishi Jin,
Andrew D. Chisholm
Affiliations
Anjali Sandhu
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Xiaohui Lyu
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Xinghaoyun Wan
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Xuefeng Meng
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Ngang Heok Tang
Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Gilberto Gonzalez
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
Ishana N. Syed
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
Lizhen Chen
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
Yishi Jin
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA
Andrew D. Chisholm
Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA; Corresponding author
Summary: The EFA6 protein family, originally identified as Sec7 guanine nucleotide exchange factors, has also been found to regulate cortical microtubule (MT) dynamics. Here, we find that in the mature C. elegans epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR). The EFA-6 IDR can form biomolecular condensates in vitro. In genetic screens for mutants with altered GFP::EFA-6 localization, we identified a gain-of-function (gf) mutation in α-tubulin tba-1 that induces ectopic EFA-6 foci in multiple cell types. Lethality of tba-1(gf) is partially suppressed by loss of function in efa-6. The ability of TBA-1(gf) to trigger ectopic EFA-6 foci requires β-tubulin TBB-2 and the chaperon EVL-20/Arl2. tba-1(gf)-induced EFA-6 foci display slower turnover, contain the MT-associated protein TAC-1/TACC, and require the EFA-6 MT elimination domain (MTED). Our results reveal functionally important crosstalk between cellular tubulins and cortical MT regulators in vivo.