Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms

Homaira Nawabi, Stephane Belin, Romain Cartoni, Philip R. Williams, Chen Wang, Alban Latremolière, Xuhua Wang, Junjie Zhu, Daniel G. Taub, Xiaoqin Fu, Bin Yu, Xiaosong Gu, Clifford J. Woolf, Judy S. Liu, Christopher V. Gabel, Judith A. Steen, Zhigang He

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


After axotomy, neuronal survival and growth cone re-formation are required for axon regeneration. We discovered that doublecortin-like kinases (DCLKs), members of the doublecortin (DCX) family expressed in adult retinal ganglion cells (RGCs), play critical roles in both processes, through distinct mechanisms. Overexpression of DCLK2 accelerated growth cone re-formation in vitro and enhanced the initiation and elongation of axon re-growth after optic nerve injury. These effects depended on both the microtubule (MT)-binding domain and the serine-proline-rich (S/P-rich) region of DCXs in-cis in the same molecules. While the MT-binding domain is known to stabilize MT structures, we show that the S/P-rich region prevents F-actin destabilization in injured axon stumps. Additionally, while DCXs synergize with mTOR to stimulate axon regeneration, alone they can promote neuronal survival possibly by regulating the retrograde propagation of injury signals. Multifunctional DCXs thus represent potential targets for promoting both survival and regeneration of injured neurons.

Original languageEnglish
Pages (from-to)704-719
Number of pages16
Issue number4
StatePublished - Nov 18 2015


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