Kavli Affiliate: Yishi Jin
| Authors: Anjali Sandhu, Xiaohui Lyu, Xinghaoyun Wan, Xuefeng Meng, Ngang Heok Tang, Gilberto Gonzalez, Ishana N Syed, Lizhen Chen, Yishi Jin and Andrew D Chisholm
| Summary:
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 of 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). In screens for mutants with aberrant GFP::EFA-6 localization, we identified a novel gain-of-function (gf) mutation in an alpha-tubulin tba-1 that induces aberrant, ectopic EFA-6 foci in multiple cell types. We further show the EFA-6 IDR is sufficient to form biomolecular condensates in vitro. 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 beta-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 but not its IDR. Our results reveal a novel crosstalk between cellular tubulins and cortical MT regulators in vivo.