TABLE 1

Summary of mutations used for epistasis analysis of the Gαq and Gαs pathways

Desired pathway
 manipulationMutation(s) or drug used
 for pathway manipulationMutation typeAffected proteinEffect of mutation or drugReference for mutation
 description
Block Gαq pathwayegl-30(ad810)Probable nullEGL-30 (Gαq)Knocks out EGL-30 (Gαq): paralysisBrundage et al. (1996)
Block Gαq pathway at
   the downstream
   synaptic vesicle
   priming mechanismunc-13(s69)Strong loss of function
   (near null)UNC-13Strongly reduces UNC-13: paralysisRichmond et al. (1999);
   Kohn et al. (2000)
Activate Gαq pathwayegl-30(tg26)Strong gain of functionEGL-30 (Gαq)Activates EGL-30 (Gαq): hyperactive
   locomotionDoi and Iwasaki (2002)
eat-16(ce71)Probable nullEAT-16 (RGS protein
   for EGL-30)Increases activity of EGL-30 (Gαq) by
   knocking out the EAT-16 RGS
   protein: hyperactive locomotionThis study
goa-1(sa734)NullGOA-1 (Gαo)Increases activity of EGL-30 pathway
   by an unknown mechanism (point
   of intersection unknown):
   hyperactive locomotionRobatzek and Thomas
   (2000)
Activate Gαq pathway at
   the downstream
   synaptic vesicle
   priming mechanismPhorbol myristate acetate
   (phorbol ester)NASynaptic vesicle
   priming proteins:
   effects require
   UNC-13Activates synaptic vesicle priming;
   bypasses the requirement for
   Gαq: hyperactive locomotionLackner et al. (1999);
   this study; see also
   Introduction for
   references
Block Gαs pathwayacy-1(pk1279)NullACY-1 (adenylyl
   cyclase)Knocks out ACY-1: near paralysisMoorman and Plasterk
   (2002)
Activate one or more
   components of the
   Gαs pathwaygsa-1(ce81)Strong gain of functionGSA-1 (Gαs)Hyperactivates Gαs by inhibiting
   GTP hydrolysis: hyperactive
   locomotionSchade et al. (2005)
gsa-1(ce94)Strongest GSA-1 gain
   of functionGSA-1 (Gαs)Strongly hyperactivates Gαs:
   hyperactive locomotionSchade et al. (2005)
acy-1(md1756)Strong gain of functionACY-1 (adenylyl
   cyclase)Activates ACY-1; probably increases
   cAMP: hyperactive locomotionSchade et al. (2005)
acy-1(ce2)Strong gain of functionACY-1 (adenylyl
   cyclase)Activates ACY-1; probably increases
   cAMP: hyperactive locomotionSchade et al. (2005)
kin-2(ce179)Strong reduction of
   functionKIN-2 (regulatory
   subunit protein
   kinase A)Makes protein kinase A holoenzyme
   extremely hypersensitive to
   cAMP: hyperactive locomotionSchade et al. (2005)
Strongly reduce receptor-independent activation
   of the Gαq pathwayric-8(md303)Strong reduction of
   functionRIC-8 (synembryn)Strongly reduces activation of the
   Gαq pathway; may also affect the
   Gαs pathway: near paralysisMiller et al. (2000);
   Schade et al. (2005)
Knock out receptor-independent activation
   of both the Gαq and
   the Gαs pathwaysric-8(ok98)NullRIC-8 (synembryn)Blocks activation of both the Gαq
   and the Gαs pathways: paralysisThis study