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

Hagiwara, A., Kitahara, Y., Grabner, C., Vogl, C., Abe, M., Kitta, R., et al. (2018). Cytomatrix proteins CAST and ELKS regulate retinal photoreceptor development and maintenance. Journal of Cell Biology, 217(11), 3993-4006. doi:10.1083/jcb.201704076.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-11C0-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-647C-2
Genre: Journal Article

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Hagiwara, A., Author
Kitahara, Y., Author
Grabner, C.1, Author              
Vogl, C., Author
Abe, M., Author
Kitta, R., Author
Ohta, K., Author
Nakamura, K., Author
Sakimura, K., Author
Moser, T.1, Author              
Nishi, A., Author
Ohtsuka, T., Author
Affiliations:
1Research Group of Synaptic Nanophysiology, MPI for Biophysical Chemistry, Max Planck Society, ou_2205655              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2018-09-062018-11-05
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1083/jcb.201704076
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Title: Journal of Cell Biology
Source Genre: Journal
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Pages: - Volume / Issue: 217 (11) Sequence Number: - Start / End Page: 3993 - 4006 Identifier: -