Phosphorylation of Doublecortin by Protein Kinase A Orchestrates Microtubule and Actin Dynamics to Promote Neuronal Progenitor Cell Migration

Toriyama, Manami; Mizuno, Norikazu; Fukami, Takashi; Iguchi, Takuma; Toriyama, Minoru; Tago, Kenji; Itoh, Hiroshi

doi:10.1074/jbc.m111.316307

Cited by 37 publications

(28 citation statements)

References 59 publications

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“…DCX is best known as a MT-binding protein, but there are also populations of DCX not bound to MTs (13,20,27). In previous work, we found that DCX-R89G, a patient allele that lacks MT binding, is still able to support NF endocytosis in PC12 cells (24).…”

Section: Ap-2 Is In a Complex With DCX That Is Not Bound To Microtubulesmentioning

confidence: 80%

A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect

Yap

Digilio

Kruczek

et al. 2018

Journal of Biological Chemistry

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Edited by Phyllis I. HansonDoublecortin (DCX) is a protein needed for cortical development, and DCX mutations cause cortical malformations in humans. The microtubule-binding activity of DCX is well-described and is important for its function, such as supporting neuronal migration and dendrite growth during development. Previous work showed that microtubule binding is not sufficient for DCX-mediated promotion of dendrite growth and that domains in DCX's C terminus are also required. The more C-terminal regions of DCX bind several other proteins, including the adhesion receptor neurofascin and clathrin adaptors. We recently identified a role for DCX in endocytosis of neurofascin. The disease-associated DCX-G253D mutant protein is known to be deficient in binding neurofascin, and we now asked if disruption of neurofascin endocytosis underlies the DCX-G253D-associated pathology. We first demonstrated that DCX functions in endocytosis as a complex with both the clathrin adaptor AP-2 and neurofascin: disrupting either clathrin adaptor binding (DCX-ALPA) or neurofascin binding (DCX-G253D) decreased neurofascin endocytosis in primary neurons. We then investigated a known function for DCX, namely, increasing dendrite growth in cultured neurons. Surprisingly, we found that the DCX-ALPA and DCX-G253D mutants yield distinct dendrite phenotypes. Unlike DCX-ALPA, DCX-G253D caused a dominant-negative dendrite growth phenotype. The endocytosis defect of DCX-G253D thus was separable from its detrimental effects on dendrite growth. We recently identified Dcx-R59H as a dominant allele and can now classify Dcx-G253D as a second Dcx allele that acts dominantly to cause pathology, but does so via a different mechanism. This article contains Fig. S1.

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Section: Ap-2 Is In a Complex With DCX That Is Not Bound To Microtubulesmentioning

confidence: 80%

A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect

Yap

Digilio

Kruczek

et al. 2018

Journal of Biological Chemistry

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“…DA signaling has also been shown to affect cellular migration of cortical GABA-ergic interneurons by modulating the cytoskeleton (reviewed in Money and Stanwood, 2013). Calcium-mediated cyclic AMP (cAMP) and protein kinase A (PKA) activation is a well-established pathway by which Ca 2+ fluxes regulate cytoskeletal remodeling and cellular migration during neuronal lamination (Toriyama et al, 2012). The nucleoskeleton-to-cytoskeleton linker complexes (LINCs) required for cone-specific cell positioning have been described (Razafsky et al, 2012; Yu et al, 2011), although whether they are disrupted when cone activity changes has yet to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

et al. 2018

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SUMMARY Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.

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“…HEK293T, MEF, and NIH3T3 cells were maintained as previously described (21). Twenty-four hours before the experiments, the cells were cultured in RPMI1640, folic-acid-free medium containing 10% dialyzed FBS.…”

Section: Cell Culture Transfection and Retrovirus Infectionmentioning

confidence: 99%

Folate‐dependent methylation of septins governs ciliogenesis during neural tube closure

Toriyama

Wallingford

et al. 2017

FASEB j.

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Periconception maternal folic acid (vitamin B) supplementation can reduce the prevalence of neural tube defects (NTDs), although just how folates benefit the developing embryo and promote closing of the neural tube and other morphologic processes during development remains unknown. Folate contributes to a 1-carbon metabolism, which is essential for purine biosynthesis and methionine recycling and affects methylation of DNA, histones, and nonhistone proteins. Herein, we used animal models and cultured mammalian cells to demonstrate that disruption of the methylation pathway mediated by folate compromises normal neural tube closure (NTC) and ciliogenesis. We demonstrate that the embryos with NTD failed to adequately methylate septin2, a key regulator of cilium structure and function. We report that methylation of septin2 affected its GTP binding activity and formation of the septin2-6-7 complex. We propose that folic acid promotes normal NTC in some embryos by regulating the methylation of septin2, which is critical for normal cilium formation during early embryonic development.-Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.

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Phosphorylation of Doublecortin by Protein Kinase A Orchestrates Microtubule and Actin Dynamics to Promote Neuronal Progenitor Cell Migration

Cited by 37 publications

References 59 publications

A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect

A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

Folate‐dependent methylation of septins governs ciliogenesis during neural tube closure

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