The C-terminus of human Ca(v)2.3 voltage-gated calcium channel interacts with alternatively spliced calmodulin-2 expressed in two human cell lines.
Ca(v)2.3 containing voltage-activated Ca(2+) channels are expressed in excitable cells and trigger neurotransmitter and peptide-hormone release. Their expression remote from the fast release sites leads to the accumulation of presynaptic Ca(2+) which can both, facilitate and inhibit the influx of Ca(2+) ions through Ca(v)2.3. The facilitated Ca(2+) influx was recently related to hippocampal postsynaptic facilitation and long term potentiation. To analyze Ca(2+) mediated modulation of cellular processes more in detail, protein partners of the carboxy terminal tail of Ca(v)2.3 were identified by yeast-2-hybrid screening, leading in two human cell lines to the detection of a novel, extended and rarely occurring splice variant of calmodulin-2 (CaM-2), called CaM-2-extended (CaM-2-ext). CaM-2-ext interacts biochemically with the C-terminus of Ca(v)2.3 similar to the classical CaM-2 as shown by co-immunoprecipitation. Functionally, only CaM-2-ext reduces whole cell inward currents significantly. The insertion of the novel 46 nts long exon and the consecutive expression of CaM-2-ext must be dependent on a new upstream translation initiation site which is only rarely used in the tested human cell lines. The structure of the N-terminal extension is predicted to be more hydrophobic than the remaining CaM-2-ext protein, suggesting that it may help to dock it to the lipophilic membrane surrounding.
Institute for Neurophysiology, University of Cologne, Germany.
Marcel A
MA
Kamp
Behzad
B
Shakeri
Etienne E
EE
Tevoufouet
Andreas
A
Krieger
Margit
M
Henry
Kerstin
K
Behnke
Stefan
S
Herzig
Jürgen
J
Hescheler
Kayalvizhi
K
Radhakrishnan
Lucie
L
Parent
Toni
T
Schneider
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data
C423009:CACNA1E protein, human; C488659:CALM2 protein, human; D020908:Calcium Channels, R-Type; D002147:Calmodulin; D027682:Cation Transport Proteins; D002118:Calcium