Calcium channel structural determinants of synaptic transmission between identified invertebrate neurons.
We report here that unlike what was suggested for many vertebrate neurons, synaptic transmission in Lymnaea stagnalis occurs independent of a physical interaction between presynaptic calcium channels and a functional complement of SNARE proteins. Instead, synaptic transmission in Lymnaea requires the expression of a C-terminal splice variant of the Lymnaea homolog to mammalian N- and P/Q-type calcium channels. We show that the alternately spliced region physically interacts with the scaffolding proteins Mint1 and CASK, and that synaptic transmission is abolished following RNA interference knockdown of CASK or after the injection of peptide sequences designed to disrupt the calcium channel-Mint1 interactions. Our data suggest that Mint1 and CASK may serve to localize the non-L-type channels at the active zone and that synaptic transmission in invertebrate neurons utilizes a mechanism for optimizing calcium entry, which occurs independently of a physical association between calcium channels and SNARE proteins.
Spafford
J David
JD
Department of Molecular and Cellular Neurobiology, Vrije Universiteit, Amsterdam, 108HV Netherlands.
Munno
David W
DW
Van Nierop
Pim
P
Feng
Zhong-Ping
ZP
Jarvis
Scott E
SE
Gallin
Warren J
WJ
Smit
August B
AB
Zamponi
Gerald W
GW
Syed
Naweed I
NI
D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000502:physiology; D017931:DNA Primers; D051528:Guanylate Kinases; D008195:Lymnaea; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009703:Nucleoside-Phosphate Kinase / Q000502:physiology; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
D015220:Calcium Channels; D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases