DCLK1 phosphorylates the microtubule‐associated protein MAP7D1 to promote axon elongation in cortical neurons

Abstract

Doublecortin-like kinase 1 (DCLK1) is a member of the neuronal microtubule-associated doublecortin (DCX) family and functions in multiple stages of neural development including radial migration and axon growth of cortical neurons. DCLK1 is suggested to play the roles in part through its protein kinase activity, yet the kinase substrates of DCLK1 remain largely unknown. Here we have identified MAP7D1 (microtubule-associated protein 7 domain containing 1) as a novel substrate of DCLK1 by using proteomic analysis. MAP7D1 is expressed in developing cortical neurons, and knockdown of MAP7D1 in layer 2/3 cortical neurons results in a significant impairment of callosal axon elongation, but not of radial migration, in corticogenesis. We have further defined the serine 315 (Ser 315) of MAP7D1 as a DCLK1-induced phosphorylation site and shown that overexpression of a phosphomimetic MAP7D1 mutant in which Ser 315 is substituted with glutamic acid (MAP7D1 S315E), but not wild-type MAP7D1, fully rescues the axon elongation defects in Dclk1 knockdown neurons. These data demonstrate that DCLK1 phosphorylates MAP7D1 on Ser 315 to facilitate axon elongation of cortical neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.

Identification of Potential Key Genes Associated With the Pathogenesis and Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis

“…AADAC is a major serine esterase that extensively implicates the hydrolysis of diverse clinical drugs, and it is highly expressed in human liver and gastrointestinal tract ( Kobayashi et al, 2012 ; Yoshida et al, 2018 ). MAP7D2 belongs to the MAP7 family of microtubule-associated proteins ( Koizumi et al, 2017 ). MAPs play a major role in numerous critical cellular and intracellular activities, such as cell division, motility, differentiation and so on ( Bhat and Setaluri, 2007 ).…”

MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon

“…All family members share a highly conserved N-terminal coiled-coil motif, which interacts with microtubules and a conserved C-terminal MAP7 coiled-coil domain that is presumed to bind to kinesin-1. MAP7 and MAP7D1 are broadly expressed and have been described to play a role in neuronal developmental processes, including in axonal development in cultured neurons ( Koizumi et al., 2017 , Tymanskyj et al., 2017 ). MAP7D2 on the other hand is predominantly expressed in brain tissues ( Niida and Yachie, 2011 ); however, little is known about its localization and function in neuronal cells.…”

Doublecortin-like Kinase 1 Regulates α-Synuclein Levels and Toxicity

“…This result suggests that Dclk1 may not directly phosphorylate ␣-Syn. This is perhaps not surprising as ␣-Syn lacks the proposed consensus motif for Dclk1 (R-R-X-X-S*/T*) (Shang et al, 2003;Koizumi et al, 2017).…”

“…The function of the kinase domain is less well characterized. MAP7D1, a microtubule binding protein, DCX, and DCLK1 itself are the only known phosphorylation targets of DCLK1 (Koizumi et al, 2017). Additionally, little is known about the function of DCLK1 in the adult brain.…”