Abstract
Cysteine string proteins (CSPs) are secretory vesicle proteins bearing a "J domain" and a palmitoylated cysteine-rich "string" region that are critical for neurotransmitter release. The precise role of CSP in neurotransmission is controversial. Here, we demonstrate a novel interaction between CSP, receptor-coupled trimeric GTP binding proteins (G proteins), and N-type Ca2+ channels. G. subunits interact with the J domain of CSP in an ATP-dependent manner; in contrast, Gbetagamma subunits interact with the C terminus of CSP in both the presence and absence of ATP. The interaction of CSP with both G proteins and N-type Ca2+ channels results in a tonic G protein inhibition of the channels. In view of the crucial importance of N-type Ca2+ channels in presynaptic vesicle release, our data attribute a key role to CSP in the fine tuning of neurotransmission.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / metabolism
-
Animals
-
Calcium Channel Blockers / pharmacology
-
Calcium Channels, N-Type / drug effects
-
Calcium Channels, N-Type / metabolism*
-
Cell Line
-
Cross-Linking Reagents / pharmacology
-
GTP-Binding Proteins / genetics
-
GTP-Binding Proteins / metabolism*
-
GTP-Binding Proteins / pharmacology
-
HSP40 Heat-Shock Proteins
-
Hippocampus / chemistry
-
Hippocampus / metabolism
-
Humans
-
Immunoblotting
-
In Vitro Techniques
-
Ion Transport / drug effects
-
Membrane Proteins / drug effects
-
Membrane Proteins / metabolism*
-
Models, Molecular
-
Patch-Clamp Techniques
-
Potassium Chloride / pharmacology
-
Protein Binding / drug effects
-
Protein Subunits
-
Rats
Substances
-
Calcium Channel Blockers
-
Calcium Channels, N-Type
-
Cross-Linking Reagents
-
HSP40 Heat-Shock Proteins
-
Membrane Proteins
-
Protein Subunits
-
cysteine string protein
-
Potassium Chloride
-
Adenosine Triphosphate
-
GTP-Binding Proteins