Abstract：
:In the presynaptic terminal, the magnitude and location of Ca2+ entry through voltage-gated Ca2+ channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein family at the calyx of Held, a CaV2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the CaV2.1 current density with concomitant reductions in CaV2.1 channel numbers and clusters. Surprisingly, deletion of CAST/ELKS increases release probability while decreasing the readily releasable pool, with no change in active zone ultrastructure. In addition, Ca2+ channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of CaV2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity.
journal_name
Cell Repjournal_title
Cell reportsauthors
Dong W,Radulovic T,Goral RO,Thomas C,Suarez Montesinos M,Guerrero-Given D,Hagiwara A,Putzke T,Hida Y,Abe M,Sakimura K,Kamasawa N,Ohtsuka T,Young SM Jrdoi
10.1016/j.celrep.2018.06.024subject
Has Abstractpub_date
2018-07-10 00:00:00pages
284-293.e6issue
2issn
2211-1247pii
S2211-1247(18)30919-7journal_volume
24pub_type
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