Cytomatrix proteins CAST and ELKS regulate retinal photoreceptor development and maintenance.

Autor:	Hagiwara A; Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan., Kitahara Y; Department of Pharmacology, Kurume University School of Medicine, Fukuoka, Japan., Grabner CP; Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center Göttingen, Göttingen, Germany.; Synaptic Nanophysiology Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany., Vogl C; Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center Göttingen, Göttingen, Germany., Abe M; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan., Kitta R; Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan., Ohta K; Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan., Nakamura K; Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan., Sakimura K; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan., Moser T; Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center Göttingen, Göttingen, Germany tmoser@gwdg.de.; Synaptic Nanophysiology Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.; Collaborative Research Center 889, University of Göttingen, Göttingen, Germany., Nishi A; Department of Pharmacology, Kurume University School of Medicine, Fukuoka, Japan., Ohtsuka T; Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan tohtsuka@yamanashi.ac.jp.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2018 Nov 05; Vol. 217 (11), pp. 3993-4006. Date of Electronic Publication: 2018 Sep 06.
DOI:	10.1083/jcb.201704076
Abstrakt:	At the presynaptic active zone (AZ), the related cytomatrix proteins CAST and ELKS organize the presynaptic release machinery. While CAST is known to regulate AZ size and neurotransmitter release, the role of ELKS and the integral system of CAST/ELKS together is poorly understood. Here, we show that CAST and ELKS have both redundant and unique roles in coordinating synaptic development, function, and maintenance of retinal photoreceptor ribbon synapses. A CAST/ELKS double knockout (dKO) mouse showed high levels of ectopic synapses and reduced responses to visual stimulation. Ectopic formation was not observed in ELKS conditional KO but progressively increased with age in CAST KO mice with higher rates in the dKO. Presynaptic calcium influx was strongly reduced in rod photoreceptors of CAST KO and dKO mice. Three-dimensional scanning EM reconstructions showed structural abnormalities in rod triads of CAST KO and dKO. Remarkably, AAV-mediated acute ELKS deletion after synapse maturation induced neurodegeneration and loss of ribbon synapses. These results suggest that CAST and ELKS work in concert to promote retinal synapse formation, transmission, and maintenance. (© 2018 Hagiwara et al.)
Databáze:	MEDLINE
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