Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization

Toriyama, Minoru; Shimada, Tadayuki; Kim, Ki Bum; Mitsuba, Mari; Nomura, Eiko; Katsuta, Kazuhiro; Sakumura, Yuichi; Roepstorff, Peter; Inagaki, Naoyuki

doi:10.1083/jcb.200604160

Cited by 141 publications

(223 citation statements)

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“…3C). We used a green volume marker, CMFDA, as an internal standard to measure relative concentration of singar (singar immunoreactivity/CMFDA staining) (24). The relative concentrations of singar in growth cones of minor processes and axons were 2.3 Ϯ 0.2 times (n ϭ 15 growth cones) and 2.9 Ϯ 0.2 times (n ϭ 15 growth cones) higher than that in cell bodies, respectively (Fig.…”

Section: Identification Of Singar1 By a Proteome Screening Of Stage 2mentioning

confidence: 99%

“…Recently, we identified the protein shootin1, which is located at an upstream position in polarity signals involving PI 3-kinase (24). Overexpression of shootin1 in hippocampal neurons leads to formation of surplus axons.…”

Section: Overexpression Of Singar1 Suppresses the Formation Of Surplumentioning

confidence: 99%

“…We screened about 6,200 protein spots on 2-DE gels and detected 277 that were consistently up-regulated during the transition between stages 2 and 3 (24). Tryptic digestion and mass spectrometry of one of them, located at a molecular mass of 55 kDa and pI ϭ 5.2 in gels (Fig.…”

Section: Identification Of Singar1 By a Proteome Screening Of Stage 2mentioning

confidence: 99%

“…Reduction in the expression or activities of glycogen synthase kinase-3␤, PTEN, or microtubule affinity-regulation kinase (MARK)2 in hippocampal neurons leads to formation of multiple axons (11,12,23), suggesting that these molecules may be involved in inhibiting the formation of surplus axons. Recently, we identified the protein shootin1, which is located upstream of PI 3-kinase and involved in neuronal polarization (24). During polarization, shootin1 accumulated in a single neurite while being depleted in its sibling neurites, through competitive transport to multiple neurites.…”

mentioning

confidence: 99%

“…During polarization, shootin1 accumulated in a single neurite while being depleted in its sibling neurites, through competitive transport to multiple neurites. This in turn induced formation of a single axon, leading us to propose that the depletion of shootin1 from the sibling neurites of the nascent axon by competition prevents the formation of surplus axons (24).…”

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confidence: 99%

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Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity

Mori

Wada

Suzuki

et al. 2007

Journal of Biological Chemistry

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Although neuronal functions depend on their robust polarity, the mechanisms that ensure generation and maintenance of only a single axon remain poorly understood. Using highly sensitive two-dimensional electrophoresis-based proteomics, we identified here a novel protein, single axon-related (singar)1/KIAA0871/RPIPx/RUFY3, which contains a RUN domain and is predominantly expressed in the brain. Singar1 expression became up-regulated during polarization of cultured hippocampal neurons and remained at high levels thereafter. Singar1 was diffusely localized in hippocampal neurons and moderately accumulated in growth cones of minor processes and axons. Overexpression of singar1 did not affect normal neuronal polarization but suppressed the formation of surplus axons induced by excess levels of shootin1, a recently identified protein located upstream of phosphoinositide-3-kinase and involved in neuronal polarization. Conversely, reduction of the expression of singar1 and its splicing variant singar2 by RNA interference led to an increase in the population of neurons bearing surplus axons, in a phosphoinositide-3-kinase-dependent manner. Overexpression of singar2 did not suppress the formation of surplus axons induced by shootin1. We propose that singar1 ensures the robustness of neuronal polarity by suppressing formation of surplus axons.Most neurons develop polarity by forming a single long axon and multiple short dendrites (1, 2). The ability of neurons to develop and maintain polarity is essential for their basic functions. The polarization processes have been extensively studied in cultured hippocampal neurons (1, 3). These cells first form several minor processes, any of which appears capable of becoming either an axon or a dendrite, during the first 12-24 h after plating (stage 2). One of the neurites then rapidly elongates to acquire axonal characteristics (stage 3), whereas the others later become dendrites (stage 4). Hippocampal neurons must use a robust internal mechanism that ensures polarization as they regenerate a single axon and multiple dendrites even when polarity is altered by axonal amputation (4, 5).Recent studies have begun to reveal molecules involved in neuronal polarization (6 -8). Localization, overexpression, and loss of function studies showed that spatially localized intracellular signals of a number of molecules, such as phosphoinositide-3-kinase (PI 3-kinase) 2 (9), phosphatidylinositol (3, 4, 5) triphosphate (10), Akt (11), glycogen synthase kinase-3␤ (11-13), collapsin response mediator protein-2 (CRMP-2) (12, 14), mPar3/mPar6/atypical protein kinase C complex (9, 15), Cdc42 (15, 16), Rap1B (16), STEF/Tiam1 (15, 17), Rac (15), adenomatous polyposis coli (18), JNK (19), and DOCK7 (20) are involved in axon specification for neuronal polarity formation. As downstream events, these pathways are thought to regulate cytoskeletal networks of actin filaments (21) and microtubules (20,22).In contrast to the progress in defining the mechanisms of axon specification, our knowledge of how neurons g...

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Section: Identification Of Singar1 By a Proteome Screening Of Stage 2mentioning

confidence: 99%

Section: Overexpression Of Singar1 Suppresses the Formation Of Surplumentioning

confidence: 99%

Section: Identification Of Singar1 By a Proteome Screening Of Stage 2mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity

Mori

Wada

Suzuki

et al. 2007

Journal of Biological Chemistry

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Neuromechanobiology: An Expanding Field Driven by the Force of Greater Focus

Motz

Kabat

Saxena

et al. 2021

Adv Healthcare Materials

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The brain processes information by transmitting signals through highly connected and dynamic networks of neurons. Neurons use specific cellular structures, including axons, dendrites and synapses, and specific molecules, including cell adhesion molecules, ion channels and chemical receptors to form, maintain and communicate among cells in the networks. These cellular and molecular processes take place in environments rich of mechanical cues, thus offering ample opportunities for mechanical regulation of neural development and function. Recent studies have suggested the importance of mechanical cues and their potential regulatory roles in the development and maintenance of these neuronal structures. Also suggested are the importance of mechanical cues and their potential regulatory roles in the interaction and function of molecules mediating the interneuronal communications. In this review, the current understanding is integrated and promising future directions of neuromechanobiology are suggested at the cellular and molecular levels. Several neuronal processes where mechanics likely plays a role are examined and how forces affect ligand binding, conformational change, and signal induction of molecules key to these neuronal processes are indicated, especially at the synapse. The disease relevance of neuromechanobiology as well as therapies and engineering solutions to neurological disorders stemmed from this emergent field of study are also discussed.

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Polymorphic variants at 10q25.3 and 17q22 loci and the risk of non‐syndromic cleft lip and palate in the polish population

Mostowska

Hozyasz

Wójcicka

et al. 2011

Birth Defects Research

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Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization

Cited by 141 publications

References 36 publications

Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity

Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity

Neuromechanobiology: An Expanding Field Driven by the Force of Greater Focus

Polymorphic variants at 10q25.3 and 17q22 loci and the risk of non‐syndromic cleft lip and palate in the polish population

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