Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior.
G-protein-coupled metabotropic glutamate group I receptors (mGluR1s) mediate synaptic transmission and plasticity in Purkinje cells and, therefore, critically determine cerebellar motor control and learning. Purkinje cells express two members of the G-protein G(q) family, namely G(q) and G11. Although in vitro coexpression of mGluR1 with either Galpha11 or Galpha(q) produces equally well functioning signaling cascades, Galpha(q)- and Galpha11-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca2+ imaging in Purkinje cells, we show that Galpha(q) is required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Galpha11 has no detectable contribution for synaptic transmission but also contributes to LTD. Quantitative single-cell RT-PCR analyses in Purkinje cells demonstrate a more than 10-fold stronger expression of Galpha(q) versus Galpha11. Our findings suggest an expression level-dependent action of Galpha(q) and Galpha11 for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination.
Hartmann
J
J
Institut für Physiologie, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Blum
R
R
Kovalchuk
Y
Y
Adelsberger
H
H
Kuner
R
R
Durand
G M
GM
Miyata
M
M
Kano
M
M
Offermanns
S
S
Konnerth
A
A
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002522:Chlorocebus aethiops; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005456:Fluorescent Dyes; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
D005456:Fluorescent Dyes; D021122:Protein Subunits; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium