| First Author | Fu X | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 2 | Pages | 709-21 |
| PubMed ID | 23303949 | Mgi Jnum | J:193908 |
| Mgi Id | MGI:5469911 | Doi | 10.1523/JNEUROSCI.4603-12.2013 |
| Citation | Fu X, et al. (2013) Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons. J Neurosci 33(2):709-21 |
| abstractText | Doublecortin (Dcx) is the causative gene for X-linked lissencephaly, which encodes a microtubule-binding protein. Axon tracts are abnormal in both affected individuals and in animal models. To determine the reason for the axon tract defect, we performed a semiquantitative proteomic analysis of the corpus callosum in mice mutant for Dcx. In axons from mice mutant for Dcx, widespread differences are found in actin-associated proteins as compared with wild-type axons. Decreases in actin-binding proteins alpha-actinin-1 and alpha-actinin-4 and actin-related protein 2/3 complex subunit 3 (Arp3), are correlated with dysregulation in the distribution of filamentous actin (F-actin) in the mutant neurons with increased F-actin around the cell body and decreased F-actin in the neurites and growth cones. The actin distribution defect can be rescued by full-length Dcx and further enhanced by Dcx S297A, the unphosphorylatable mutant, but not with the truncation mutant of Dcx missing the C-terminal S/P-rich domain. Thus, the C-terminal region of Dcx dynamically regulates formation of F-actin features in developing neurons, likely through interaction with spinophilin, but not through alpha-actinin-4 or Arp3. We show with that the phenotype of Dcx/Doublecortin-like kinase 1 deficiency is consistent with actin defect, as these axons are selectively deficient in axon guidance, but not elongation. |
