Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 513, Issue 3, Pages 540-545Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.04.005
Keywords
Doublecortin X; Pathogenic mutant; Cytoskeleton; Microtubule dynamics
Categories
Funding
- University of Melbourne
- ARC Future Fellowship [FT120100193]
Ask authors/readers for more resources
Mutations of the microtubule (MT)-associated protein Doublecortin X (DCX) gene disrupt cortical layering in brain development. Whilst many of these pathogenic DCX mutations are within the doublecortin domains (DC1 and DC2) that mediate direct DCX-MT association, a pathogenic mutation DCX E2K that causes cognitive impairment and pachygyria in human patients lies within the regulatory DCX N-terminus (DCX-N) preceding the DC1 domain. Here, we characterise the impact of DCX E2K on cytoskeletal association and regulation in neuronal cells. We show that the DCX E2K mutant protein retains the ability to interact with and bundle MTs, but these MTs show a reduced sensitivity to nocodazole-induced depolymerisation as well as slower alpha-tubulin exchange rates. Furthermore, we showed increased association of DCX E2K mutant with the actin filament (F-ACT) network. These results highlight the importance of the N-terminus of DCX in regulating association and co-ordination of MT and F-ACT networks. (C) 2019 Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available