Extracellular and Intracellular Signaling for Neuronal Polarity

Namba, Tsuneo; Funahashi, Yasuhiro; Nakamuta, Shinichi; Xu, Chengpei; Takano, Tetsuya; Kaibuchi, Kozo

doi:10.1152/physrev.00025.2014

Cited by 98 publications

(122 citation statements)

References 382 publications

(577 reference statements)

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“…Pyramidal neurons first extend multiple minor processes and are called multipolar (MP) cells in intermediate zone (IZ). These MP cells subsequently transform into bipolar (BP) cells with a trailing process and a leading process, which finally develop into an axon and a dendrite, respectively 2, 3 . BP cells are completely polarized and migrate toward the cortical plate (CP).…”

Section: Resultsmentioning

confidence: 99%

Discovery of long-range inhibitory signaling to ensure single axon formation

et al. 2017

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A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca2+ waves, which are delivered from the growing axon to the cell body. These Ca2+ waves increase RhoA activity in the cell body through calcium/calmodulin-dependent protein kinase I. Optogenetic control of Rho-kinase combined with computational modeling reveals that active Rho-kinase diffuses to growing other immature neurites and inhibits their outgrowth. Mechanistically, calmodulin-dependent protein kinase I phosphorylates a RhoA-specific GEF, GEF-H1, whose phosphorylation enhances its GEF activity. Thus, our results reveal that long-range inhibitory signaling mediated by Ca2+ wave is responsible for neuronal polarization.

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Section: Resultsmentioning

confidence: 99%

Discovery of long-range inhibitory signaling to ensure single axon formation

et al. 2017

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“…Rho-kinase phosphorylates MYPT1 and inactivates myosin light chain phosphatase, thereby increasing the phosphorylation of MLC followed by smooth muscle contraction (Amano et al, 2010a). For the last 10 years, many substrates of Rho-kinase were studied in neurons, and it was observed that the phosphorylated proteins control nerve axon extension (Namba et al, 2015). In contrast to vascular cells and neuronal cells, less is known about the substrates of Rho-kinase in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart

Yura

Amano

Takefuji

et al. 2016

Cell Struct. Funct.

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ABSTRACT. Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography. First, we examined protein phosphorylation by extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), which has been relatively well studied in cardiomyocytes. The KISS method showed that ERK and PKA mediated the phosphorylation of known cardiac-substrates of each kinase such as Rps6ka1 and cTnI, respectively. Using this method, we found about 330 proteins as Rho-kinase-mediated substrates, whose substrate in cardiomyocytes is unknown. Among them, CARP/Ankrd1, a muscle ankyrin repeat protein, was confirmed as a novel Rho-kinasemediated substrate. We also found that non-phosphorylatable form of CARP repressed cardiac hypertrophyrelated gene Myosin light chain-2v (MLC-2v) promoter activity, and decreased cell size of heart derived H9c2 myoblasts more efficiently than wild type-CARP. Thus, focused proteomics enable us to reveal a novel signaling pathway in the heart.

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“…Nascent projection neurons are embedded in a heterogeneous environment and cell-cell interactions are likely to play an important role in neuronal polarization (Jossin, 2011; Gartner et al, 2015; Namba et al, 2015). It has been suggested that the radial glial scaffold, on which neurons perform locomotion in the IZ, could be involved in the MP-to-BP transition.…”

Section: Extracellular Cues Controlling Projection Neuron Polarity Inmentioning

confidence: 99%

“…In such context, it has been proposed that the interaction of multipolar cells and RGPs mediated by N-cadherin leads to the establishment of axon-dendrite polarity through polarized distribution of active RhoA in the neurite contacting the RGC and active Rac1 on the opposite side where the axon is formed (Xu et al, 2015). Physical interactions between pioneering axons from earlier generated neurons and the dynamic neurites from newly born neurons have been shown to contribute to polarization in MP neurons (Namba et al, 2014, 2015). These interactions involve the cell adhesion molecule transient axonal glycoprotein 1 (TAG-1).…”

Section: Extracellular Cues Controlling Projection Neuron Polarity Inmentioning

confidence: 99%

Cell Polarity in Cerebral Cortex Development—Cellular Architecture Shaped by Biochemical Networks

Hansen

Duellberg

Mieck

et al. 2017

Front. Cell. Neurosci.

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The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review article we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.

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Extracellular and Intracellular Signaling for Neuronal Polarity

Cited by 98 publications

References 382 publications

Discovery of long-range inhibitory signaling to ensure single axon formation

Discovery of long-range inhibitory signaling to ensure single axon formation

Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart

Cell Polarity in Cerebral Cortex Development—Cellular Architecture Shaped by Biochemical Networks

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