2024年 新着論文 24 病態シグナル学分野から論文が発表されました

 

Necl-1/CADM3 regulates cone synapse formation in the mouse retina

iScience. 2024 Mar 26;27(4):109577. doi: 10.1016/j.isci.2024.109577. eCollection 2024 Apr 19.

Authors

Rumi Kawashima  1 Kenji Matsushita  1 Kenji Mandai  2   3   4 Yuko Sugita  5 Tomohiko Maruo  2   3 Kiyohito Mizutani  2   6 Yoshihiro Midoh  7 Akiko Oguchi  8 Yasuhiro Murakawa  8 Kazuki Kuniyoshi  9 Ryohei Sato  10 Takahisa Furukawa  5 Kohji Nishida  1 Yoshimi Takai  2

Affiliations

  • 1 Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
  • 2 Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0047, Japan.
  • 3 Department of Molecular and Cellular Neurobiology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
  • 4 Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
  • 5 Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
  • 6 Division of Pathogenetic Signaling, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
  • 7 Graduate School of Information Science and Technology, Osaka University, Suita, Osaka 565-0871, Japan.
  • 8 RIKEN-IFOM Joint Laboratory for Cancer Genomics, IMS RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
  • 9 Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan.
  • 10 Forefront Research Center for Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.

Abstract

In vertebrates, retinal neural circuitry for visual perception is organized in specific layers. The outer plexiform layer is the first synaptic region in the visual pathway, where photoreceptor synaptic terminals connect with bipolar and horizontal cell processes. However, molecular mechanisms underlying cone synapse formation to mediate OFF pathways remain unknown. This study reveals that Necl-1/CADM3 is localized at S- and S/M-opsin-containing cones and dendrites of type 4 OFF cone bipolar cells (CBCs). In Necl-1-/- mouse retina, synapses between cones and type 4 OFF CBCs were dislocated, horizontal cell distribution became abnormal, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors were dislocated. Necl-1-/- mice exhibited aberrant short-wavelength-light-elicited signal transmission from cones to OFF CBCs, which was rescued by AMPA receptor potentiator. Additionally, Necl-1-/- mice showed impaired optokinetic responses. These findings suggest that Necl-1 regulates cone synapse formation to mediate OFF cone pathways elicited by short-wavelength light in mouse retina.

Keywords: Biological sciences; Molecular neuroscience; Neuroscience;.

Conflict of interest statement

The authors declare no competing interests.