Control of growth cone motility and neurite outgrowth by SPIN90

Kim, Seon-Myung; Bae, Jeomil; Cho, In Ha; Choi, Kyu Yeong; Park, Yeon Jung; Ryu, Je‐Hwang; Chun, Jang‐Soo; Song, Woo Keun

doi:10.1016/j.yexcr.2011.06.018

Cited by 10 publications

(10 citation statements)

References 54 publications

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“…Rabbit anti-SPIN90 polyclonal serum has been described previously [25]. Rabbit polyclonal antibodies were used to detect EGFR and phospho-EGFR (Santa Cruz Biotechnology, Texas, USA).…”

Section: Methodsmentioning

confidence: 99%

SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

Kim

Chung

et al. 2013

PLoS ONE

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The finding that SPIN90 colocalizes with epidermal growth factor (EGF) in EEA1-positive endosomes prompted us to investigate the role of SPIN90 in endocytosis of the EGF receptor (EGFR). In the present study, we demonstrated that SPIN90 participates in the early stages of endocytosis, including vesicle formation and trafficking. Stable HeLa cells with knockdown of SPIN90 displayed significantly higher levels of surface EGFR than control cells. Analysis of the abundance and cellular distribution of EGFR via electron microscopy revealed that SPIN90 knockdown cells contain residual EGFR at cell membranes and fewer EGFR-containing endosomes, both features that reflect reduced endosome formation. The delayed early endosomal targeting capacity of SPIN90 knockdown cells led to increased EGFR stability, consistent with the observed accumulation of EGFR at the membrane. Small endosome sizes and reduced endosome formation in SPIN90 knockdown cells, observed using fluorescent confocal microscopy, strongly supported the involvement of SPIN90 in endocytosis of EGFR. Overexpression of SPIN90 variants, particularly the SH3, PRD, and CC (positions 643 - 722) domains, resulted in aberrant morphology of Rab5-positive endosomes (detected as small spots located near the cell membrane) and defects in endosomal movement. These findings clearly suggest that SPIN90 participates in the formation and movement of endosomes. Consistent with this, SPIN90 knockdown enhanced cell proliferation. The delay in EGFR endocytosis effectively increased the levels of endosomal EGFR, which triggered activation of ERK1/2 and cell proliferation via upregulation of cyclin D1. Collectively, our findings suggest that SPIN90 contributes to the formation and movement of endosomal vesicles, and modulates the stability of EGFR protein, which affects cell cycle progression via regulation of the activities of downstream proteins, such as ERK1/2, after EGF stimulation.

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“…Rabbit anti-SPIN90 polyclonal serum has been described previously [25]. Rabbit polyclonal antibodies were used to detect EGFR and phospho-EGFR (Santa Cruz Biotechnology, Texas, USA).…”

Section: Methodsmentioning

confidence: 99%

SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

Kim

Chung

et al. 2013

PLoS ONE

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“…However, a role for Arp2/3 in mediating the entirety of filament nucleation should not be readily discounted, as recent work has determined that the Arp2/3 complex can be activated to nucleate filaments independent of pre-existing filaments when the complex is activated by binding to WISH/DIP1/SPIN90 (Wagner et al, 2013). SPIN90 is expressed by neurons, localizes to axons and positively regulates the number of growth cone filopodia (Kim et al, 2011). Given the relatively large cohort of identified actin filament nucleation systems, elucidation of the ones relevant to axon branching will be a fruitful venue of future research.…”

Section: Cytoskeletal Dynamics and Reorganization Underlying The Earlmentioning

confidence: 99%

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Armijo-Weingart

Gallo

2017

Molecular and Cellular Neuroscience

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The formation of axon collateral branches from the pre-existing shafts of axons is an important aspect of neurodevelopment and the response of the nervous system to injury. This article provides an overview of the role of the cytoskeleton and signaling mechanisms in the formation of axon collateral branches. Both the actin filament and microtubule components of the cytoskeleton are required for the formation of axon branches. Recent work has begun to shed light on how these two elements of the cytoskeleton are integrated by proteins that functionally or physically link the cytoskeleton. While a number of signaling pathways have been determined as having a role in the formation of axon branches, the complexity of the downstream mechanisms and links to specific signaling pathways remain to be fully determined. The regulation of intra-axonal protein synthesis and organelle function are also emerging as components of signal-induced axon branching. Although much has been learned in the last couple of decades about the mechanistic basis of axon branching we can look forward to continue elucidating this complex biological phenomenon with the aim of understanding how multiple signaling pathways, cytoskeletal regulators and organelles are coordinated locally along the axon to give rise to a branch.

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“…Experiments using fluorescent dyes or forster resonance energy transfer-based biosensors will be useful in the elucidation of the intracellular signaling pathways involved in sensing and repair of axonal damage. 32 In addition, several inhibitors, such as cytochalasin D, 33 Nocodazole, 34 and ROCK, 35 will be used in future studies involving cytoskeletal remodeling following laser subaxotomy. In conclusion, laser subaxotomy at the single-cell level can contribute to an understanding of the repair mechanism necessary to restore damaged neuronal circuits at the tissue and organ levels.…”

Section: Resultsmentioning

confidence: 99%

Rat embryonic hippocampus and induced pluripotent stem cell derived cultured neurons recover from laser-induced subaxotomy

et al. 2015

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Abstract. Axonal injury and stress have long been thought to play a pathogenic role in a variety of neurodegenerative diseases. However, a model for studying single-cell axonal injury in mammalian cells and the processes of repair has not been established. The purpose of this study was to examine the response of neuronal growth cones to laser-induced axonal damage in cultures of embryonic rat hippocampal neurons and induced pluripotent stem cell (iPSC) derived human neurons. A 532-nm pulsed Nd∶YVO 4 picosecond laser was focused to a diffraction limited spot at a precise location on an axon using a laser energy/power that did not rupture the cell membrane (subaxotomy). Subsequent time series images were taken to follow axonal recovery and growth cone dynamics. After laser subaxotomy, axons thinned at the damage site and initiated a dynamic cytoskeletal remodeling process to restore axonal thickness. The growth cone was observed to play a role in the repair process in both hippocampal and iPSC-derived neurons. Immunofluorescence staining confirmed structural tubulin damage and revealed initial phases of actin-based cytoskeletal remodeling at the damage site. The results of this study indicate that there is a repeatable and cross-species repair response of axons and growth cones after laser-induced damage.

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Control of growth cone motility and neurite outgrowth by SPIN90

Cited by 10 publications

References 54 publications

SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Rat embryonic hippocampus and induced pluripotent stem cell derived cultured neurons recover from laser-induced subaxotomy

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