Nina Wettschureck and Stefan Offermanns - Physiological Reviews
Nina Wettschureck and Stefan Offermanns - Physiological Reviews
Nina Wettschureck and Stefan Offermanns - Physiological Reviews
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1164 NINA WETTSCHURECK AND STEFAN OFFERMANNS<br />
TABLE 2. Heterotrimeric G proteins<br />
Name Gene Expression Effector(s)<br />
�-Subunits<br />
G�s class<br />
G�s GNAS Ubiquitous AC (all types) 1<br />
G�sXL (GNASXL) Neuroendocrine AC 1<br />
G�olf GNAL Olfactory epithelium, brain AC 1<br />
G�i/o class<br />
G�i1 GNAI1 Widely distributed AC (types I,III,V,VI,VIII,IX) 2 (directly regulated)<br />
G�i2 GNAI2 Ubiquitous<br />
various other effectots are regulated via G��<br />
G�i3 G�o G�z G�gust G�t-r G�t-c G�q/11 class<br />
G�q G�11 G�14 G�15/16 G�12/13 class<br />
G�12 G�13 �-Subunits<br />
GNAI3<br />
GNAO<br />
GNAZ<br />
GNAT3<br />
GNAT1<br />
GNAT2<br />
GNAQ<br />
GNA11<br />
GNA14<br />
GNA16 (Gna15)<br />
GNA12<br />
GNA13<br />
Widely distributed<br />
Neuronal, neuroendocrine<br />
Neuronal, platelets<br />
Taste cells, brush cells<br />
Retinal rods, taste cells<br />
Retinal cones<br />
Ubiquitous<br />
Almost ubiquitous<br />
Kidney, lung, spleen<br />
Hematopoietic cells<br />
Ubiquitous<br />
Ubiquitous<br />
released from activated Gi1-3 (see below)<br />
VDCC2, GIRK1 (via G��; see below)<br />
AC (e.g., V,VI) 2 (directly regulated); Rap1GAP<br />
PDE 1?; other effectors via G��?<br />
PDE 6 (�-subunit rod) 1<br />
PDE 6 (�-subunit cone) 1<br />
PLC-�1-4 1<br />
PLC-�1-4 1<br />
PLC-�1-4 1<br />
PLC-�1-4 1<br />
PDZ-RhoGEF/LARG, Btk, Gap1m, cadherin<br />
p115RhoGEF, PDZ-RhoGEF/LARG, radixin<br />
�1 GNB1 Widely, retinal rods AC type I 2 AC types II,IV,VII 1 PLC-�<br />
�2 GNB2 Widely distributed<br />
(�3��2��1) 1 GIRK1–4 (Kir3.1–3.4) 1 receptor<br />
�3 GNB3 Widely, retinal cones<br />
kinases (GRK 2 <strong>and</strong> 3) 1 PI-3-K, �, � 1 T type<br />
�4 �5 �-Subunits<br />
GNB4<br />
GNB5<br />
Widely distributed<br />
Mainly brain<br />
VDCC (Cav3.2) 2 (G�2�2) N-,P/Q-,R-type VDCC<br />
(Cav2.1–2.3) 2<br />
�1, �rod GNGT1 Retinal rods, brain,<br />
�14, �cone GNGT2 Retinal cones, brain<br />
�2, �6 GNG2 Widely<br />
�3 GNG3 Brain, blood<br />
�4 GNG4 Brain <strong>and</strong> other tissues<br />
�5 GNG5 Widely<br />
�7 GNG7 Widely<br />
�8, �9 GNG8 Olfactory/vomeronasal epithelium<br />
�10 GNG10 Widely<br />
�11 GNG11 Widely<br />
�12 GNG12 Widely<br />
�13 GNG13 Brain, taste buds<br />
AC, adenylyl cyclase; PDE, phosphodiesterase; PLC, phospholipase C; GIRK, G protein-regulated inward rectifier potassium channel; VDCC,<br />
voltage-dependent Ca 2� channel; PI-3-K, phosphatidylinositol 3-kinase; GRK, G protein-regulated kinase; RhoGEF, Rho guanine nucleotide exchange<br />
factor.<br />
high, their receptor-dependent activation results in the<br />
release of relatively high amounts of ��-complexes.<br />
Activation of G i/G o is therefore believed to be the major<br />
coupling mechanism that results in the activation of<br />
��-mediated signaling processes (112, 543). The function<br />
of members of the G i/G o family has often been<br />
studied using a toxin from Clostridium botulinum<br />
(pertussis toxin; PTX) which is able to ADP-ribosylate<br />
most of the members of the G� i/G� o family close to<br />
their COOH termini. COOH-terminally ADP-ribosylated<br />
G� i/G� o is unable to interact with the receptor. Thus<br />
PTX treatment results in the uncoupling of the receptor<br />
<strong>and</strong> G i/G o. The structural similarity between the 3 G� i<br />
subforms suggests that they may have partially overlapping<br />
functions. In contrast to other G proteins, the<br />
effects of G o, which is particularly abundant in the<br />
Physiol Rev • VOL 85 • OCTOBER 2005 • www.prv.org<br />
nervous system, appears to be primarily mediated by its<br />
��-complex. Whether G� o can regulate effectors directly<br />
is currently not clear. A less widely expressed<br />
member of the G� i/G� o family is G� z (438), which in<br />
contrast to G i <strong>and</strong> G o is not a substrate for PTX. G� z is<br />
expressed in various tissues including the nervous system<br />
<strong>and</strong> platelets. It shares some functional similarities<br />
with G i-type G proteins but has recently been shown to<br />
interact specifically with various other proteins including<br />
Rap1GAP <strong>and</strong> certain RGS proteins (438). Several<br />
�-subunits like gustducin <strong>and</strong> transducins belong to the<br />
G� i/G� o family <strong>and</strong> are involved in specific sensory<br />
functions (24, 126).<br />
The G q/G 11 family of G proteins couples receptors to<br />
�-isoforms of phospholipase C (169, 538). The �-subunits<br />
of G q <strong>and</strong> G 11 are almost ubiquitously expressed while the