A crucial role for Arf6 in the response of commissural axons to Slit

Mariko Kinoshita-Kawada, Hiroshi Hasegawa, Tsunaki Hongu, Shigeru Yanagi, Yasunori Kanaho, Ichiro Masai, Takayasu Mishima, Xiaoping Chen, Yoshio Tsuboi, Yi Rao, Junichi Yuasa-Kawada*, Jane Wu

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A switch in the response of commissural axons to the repellent Slit is crucial for ensuring that they cross the ventral midline only once. However, the underlyingmechanisms remain to be elucidated.We have found that both endocytosis and recycling of Robo1 receptor are crucial for modulating Slit sensitivity in vertebrate commissural axons. Robo1 endocytosis and its recycling back to the cell surface maintained the stability of axonal Robo1 during Slit stimulation. We identified Arf6 guanosine triphosphatase and its activators, cytohesins, as previously unknowncomponents inSlit-Robo1 signalling in vertebrate commissural neurons. Slit-Robo1 signalling activated Arf6. The Arf6-deficient mice exhibited marked defects in commissural axon midline crossing. Our data showed that a Robo1 endocytosis-triggered and Arf6-mediated positive-feedback strengthens the Slit response in commissural axons upon their midline crossing. Furthermore, the cytohesin-Arf6 pathways modulated this self-enhancement of the Slit response before and after midline crossing, resulting in a switch that reinforced robust regulation of axon midline crossing. Our study provides insights into endocytic trafficking-mediated mechanisms for spatiotemporally controlled axonal responses and uncovers new players in the midline switch in Slit responsiveness of commissural axons.

Original languageEnglish (US)
Article numberdev172106
JournalDevelopment (Cambridge)
Volume146
Issue number3
DOIs
StatePublished - Feb 1 2019

Fingerprint

Axons
Endocytosis
Recycling
Vertebrates
Guanosine
Neurons

Keywords

  • Arf6
  • Axon guidance
  • Commissural neurons
  • Endocytic recycling
  • Midline
  • Slit-Robo

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Kinoshita-Kawada, M., Hasegawa, H., Hongu, T., Yanagi, S., Kanaho, Y., Masai, I., ... Wu, J. (2019). A crucial role for Arf6 in the response of commissural axons to Slit. Development (Cambridge), 146(3), [dev172106]. https://doi.org/10.1242/dev.172106
Kinoshita-Kawada, Mariko ; Hasegawa, Hiroshi ; Hongu, Tsunaki ; Yanagi, Shigeru ; Kanaho, Yasunori ; Masai, Ichiro ; Mishima, Takayasu ; Chen, Xiaoping ; Tsuboi, Yoshio ; Rao, Yi ; Yuasa-Kawada, Junichi ; Wu, Jane. / A crucial role for Arf6 in the response of commissural axons to Slit. In: Development (Cambridge). 2019 ; Vol. 146, No. 3.
@article{14f75b81030440c5a7ffdface39c2dc7,
title = "A crucial role for Arf6 in the response of commissural axons to Slit",
abstract = "A switch in the response of commissural axons to the repellent Slit is crucial for ensuring that they cross the ventral midline only once. However, the underlyingmechanisms remain to be elucidated.We have found that both endocytosis and recycling of Robo1 receptor are crucial for modulating Slit sensitivity in vertebrate commissural axons. Robo1 endocytosis and its recycling back to the cell surface maintained the stability of axonal Robo1 during Slit stimulation. We identified Arf6 guanosine triphosphatase and its activators, cytohesins, as previously unknowncomponents inSlit-Robo1 signalling in vertebrate commissural neurons. Slit-Robo1 signalling activated Arf6. The Arf6-deficient mice exhibited marked defects in commissural axon midline crossing. Our data showed that a Robo1 endocytosis-triggered and Arf6-mediated positive-feedback strengthens the Slit response in commissural axons upon their midline crossing. Furthermore, the cytohesin-Arf6 pathways modulated this self-enhancement of the Slit response before and after midline crossing, resulting in a switch that reinforced robust regulation of axon midline crossing. Our study provides insights into endocytic trafficking-mediated mechanisms for spatiotemporally controlled axonal responses and uncovers new players in the midline switch in Slit responsiveness of commissural axons.",
keywords = "Arf6, Axon guidance, Commissural neurons, Endocytic recycling, Midline, Slit-Robo",
author = "Mariko Kinoshita-Kawada and Hiroshi Hasegawa and Tsunaki Hongu and Shigeru Yanagi and Yasunori Kanaho and Ichiro Masai and Takayasu Mishima and Xiaoping Chen and Yoshio Tsuboi and Yi Rao and Junichi Yuasa-Kawada and Jane Wu",
year = "2019",
month = "2",
day = "1",
doi = "10.1242/dev.172106",
language = "English (US)",
volume = "146",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "3",

}

Kinoshita-Kawada, M, Hasegawa, H, Hongu, T, Yanagi, S, Kanaho, Y, Masai, I, Mishima, T, Chen, X, Tsuboi, Y, Rao, Y, Yuasa-Kawada, J & Wu, J 2019, 'A crucial role for Arf6 in the response of commissural axons to Slit', Development (Cambridge), vol. 146, no. 3, dev172106. https://doi.org/10.1242/dev.172106

A crucial role for Arf6 in the response of commissural axons to Slit. / Kinoshita-Kawada, Mariko; Hasegawa, Hiroshi; Hongu, Tsunaki; Yanagi, Shigeru; Kanaho, Yasunori; Masai, Ichiro; Mishima, Takayasu; Chen, Xiaoping; Tsuboi, Yoshio; Rao, Yi; Yuasa-Kawada, Junichi; Wu, Jane.

In: Development (Cambridge), Vol. 146, No. 3, dev172106, 01.02.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A crucial role for Arf6 in the response of commissural axons to Slit

AU - Kinoshita-Kawada, Mariko

AU - Hasegawa, Hiroshi

AU - Hongu, Tsunaki

AU - Yanagi, Shigeru

AU - Kanaho, Yasunori

AU - Masai, Ichiro

AU - Mishima, Takayasu

AU - Chen, Xiaoping

AU - Tsuboi, Yoshio

AU - Rao, Yi

AU - Yuasa-Kawada, Junichi

AU - Wu, Jane

PY - 2019/2/1

Y1 - 2019/2/1

N2 - A switch in the response of commissural axons to the repellent Slit is crucial for ensuring that they cross the ventral midline only once. However, the underlyingmechanisms remain to be elucidated.We have found that both endocytosis and recycling of Robo1 receptor are crucial for modulating Slit sensitivity in vertebrate commissural axons. Robo1 endocytosis and its recycling back to the cell surface maintained the stability of axonal Robo1 during Slit stimulation. We identified Arf6 guanosine triphosphatase and its activators, cytohesins, as previously unknowncomponents inSlit-Robo1 signalling in vertebrate commissural neurons. Slit-Robo1 signalling activated Arf6. The Arf6-deficient mice exhibited marked defects in commissural axon midline crossing. Our data showed that a Robo1 endocytosis-triggered and Arf6-mediated positive-feedback strengthens the Slit response in commissural axons upon their midline crossing. Furthermore, the cytohesin-Arf6 pathways modulated this self-enhancement of the Slit response before and after midline crossing, resulting in a switch that reinforced robust regulation of axon midline crossing. Our study provides insights into endocytic trafficking-mediated mechanisms for spatiotemporally controlled axonal responses and uncovers new players in the midline switch in Slit responsiveness of commissural axons.

AB - A switch in the response of commissural axons to the repellent Slit is crucial for ensuring that they cross the ventral midline only once. However, the underlyingmechanisms remain to be elucidated.We have found that both endocytosis and recycling of Robo1 receptor are crucial for modulating Slit sensitivity in vertebrate commissural axons. Robo1 endocytosis and its recycling back to the cell surface maintained the stability of axonal Robo1 during Slit stimulation. We identified Arf6 guanosine triphosphatase and its activators, cytohesins, as previously unknowncomponents inSlit-Robo1 signalling in vertebrate commissural neurons. Slit-Robo1 signalling activated Arf6. The Arf6-deficient mice exhibited marked defects in commissural axon midline crossing. Our data showed that a Robo1 endocytosis-triggered and Arf6-mediated positive-feedback strengthens the Slit response in commissural axons upon their midline crossing. Furthermore, the cytohesin-Arf6 pathways modulated this self-enhancement of the Slit response before and after midline crossing, resulting in a switch that reinforced robust regulation of axon midline crossing. Our study provides insights into endocytic trafficking-mediated mechanisms for spatiotemporally controlled axonal responses and uncovers new players in the midline switch in Slit responsiveness of commissural axons.

KW - Arf6

KW - Axon guidance

KW - Commissural neurons

KW - Endocytic recycling

KW - Midline

KW - Slit-Robo

UR - http://www.scopus.com/inward/record.url?scp=85061140758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061140758&partnerID=8YFLogxK

U2 - 10.1242/dev.172106

DO - 10.1242/dev.172106

M3 - Article

C2 - 30674481

AN - SCOPUS:85061140758

VL - 146

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 3

M1 - dev172106

ER -

Kinoshita-Kawada M, Hasegawa H, Hongu T, Yanagi S, Kanaho Y, Masai I et al. A crucial role for Arf6 in the response of commissural axons to Slit. Development (Cambridge). 2019 Feb 1;146(3). dev172106. https://doi.org/10.1242/dev.172106