Bacteria deliver a microtubule-binding protein into mammalian cells to promote colonization - Science | AAAS

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply. AbstractFunctional recovery after spinal cord injury (SCI) remains challenging, requiring therapeutic targets. Here, we show that doublecortin-like kinase 1 (DCLK1) is upregulated after SCI in mice. Pharmacological inhibition of DCLK1 with DCLK1-IN-1 improved motor recovery, reduced glial scar formation and fibrosis, and preserved neurons at the lesion site. Mechanistically, we identified the microtubule-severing protein KATNA1 as a downstream target of DCLK1. DCLK1 directly phosphorylated KATNA1 at threonine 118 (T118), suppressing its microtubule-severing activity. DCLK1 overexpression inhibited, whereas DCLK1 knockdown or inhibition enhanced KATNA1 function. The T118D mutation reduced KATNA1 activity, while T118A resisted DCLK1-mediated suppression. In neurons, DCLK1 inhibited KATNA1-induced neurite outgrowth, whereas DCLK1 inhibition restored this effect.

AcknowledgementsWe thank Julia Nelson, Animal Disease Research and Diagnostic Laboratory, South Dakota for the help with 16S sequencing, and Metabolon, Inc. for the untargeted metabolomics. Metagenome data analysis for this project was performed using the OU Supercomputing Center for Education & Research (OSCER) at the University of Oklahoma (OU). We thank Suryang Kwak and Joohee Choi for their help in providing further details on their dataset:54. FundingThis project has received funding from the United States National Institutes of Health (contract no: G- 202306-70697), Walter R. Sitlington Endowment (grant no: 5- 153200), European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant no. 866028) and from the UK Medical Research Council (project no. MC_UU_00025/11).