Academic Journal
Presynaptic development is controlled by the core active zone proteins CAST/ELKS
| العنوان: | Presynaptic development is controlled by the core active zone proteins CAST/ELKS |
|---|---|
| المؤلفون: | Radulovic, Tamara, Dong, Wei, Goral, R. Oliver, Thomas, Connon I., Veeraraghavan, Priyadharishini, Montesinos, Monica Suarez, Guerrero‐Given, Debbie, Goff, Kevin, Lübbert, Matthias, Kamasawa, Naomi, Ohtsuka, Toshihisa, Young, Samuel M. |
| المساهمون: | National Institute of Neurological Disorders and Stroke, Max-Planck-Gesellschaft, University of Iowa, Department of Science and Technology of Sichuan Province, National Natural Science Foundation of China, Japan Society for the Promotion of Science, National Institute on Deafness and Other Communication Disorders |
| المصدر: | The Journal of Physiology ; volume 598, issue 12, page 2431-2452 ; ISSN 0022-3751 1469-7793 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2020 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Key points CAST/ELKS are positive regulators of presynaptic growth and are suppressors of active zone expansion at the developing mouse calyx of Held. CAST/ELKS regulate all three Ca V 2 subtype channel levels in the presynaptic terminal and not just Ca V 2.1. The half‐life of ELKS is on the timescale of days and not weeks. Synaptic transmission was not impacted by the loss of CAST/ELKS. CAST/ELKS are involved in pathways regulating morphological properties of presynaptic terminals during an early stage of circuit maturation. Abstract Many presynaptic active zone (AZ) proteins have multiple regulatory roles that vary during distinct stages of neuronal circuit development. The CAST/ELKS protein family are evolutionarily conserved presynaptic AZ molecules that regulate presynaptic calcium channels, synaptic transmission and plasticity in the mammalian CNS. However, how these proteins regulate synapse development and presynaptic function in a developing neuronal circuit in its native environment is unclear. To unravel the roles of CAST/ELKS in glutamatergic synapse development and in presynaptic function, we used CAST knockout (KO) and ELKS conditional KO (CKO) mice to examine how their loss during the early stages of circuit maturation impacted the calyx of Held presynaptic terminal development and function. Morphological analysis from confocal z‐stacks revealed that combined deletion of CAST/ELKS resulted in a reduction in the surface area and volume of the calyx. Analysis of AZ ultrastructure showed that AZ size was increased in the absence of CAST/ELKS. Patch clamp recordings demonstrated a reduction of all presynaptic Ca V 2 channel subtype currents that correlated with a loss in presynaptic Ca V 2 channel numbers. However, these changes did not impair synaptic transmission and plasticity and synaptic vesicle release kinetics. We conclude that CAST/ELKS proteins are positive regulators of presynaptic growth and are suppressors of AZ expansion and Ca V 2 subtype currents and levels during calyx of Held ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1113/jp279736 |
| DOI: | 10.1113/JP279736 |
| الاتاحة: | http://dx.doi.org/10.1113/jp279736 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2FJP279736 https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP279736 https://onlinelibrary.wiley.com/doi/full-xml/10.1113/JP279736 https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP279736 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.9B64CE55 |
| قاعدة البيانات: | BASE |
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