The cell migration gene
mig-2 encodes a new member of the Rho family of small GTPases, proteins that can regulate actin-dependent processes in vitro and in vivo. Putative activated alleles of
mig-2 (
rh17 and
gm38) shorten many cell migrations and cause defects in axon growth and behavior, while
mig-2 null mutations shorten only a few cell migrations, including the migrations of neuroblasts in the QR lineage. QueeLim Ch'ng and Mary Sym recently carried out a large-scale EMS screen for Q-cell migration mutants. One mutant,
mu337, was strikingly similar to activated
mig-2 mutants: in
mu337 animals the migrations of CAN, HSN, ALM and the QR descendants are shortened. Moreover, like
mig-2(
rh17),
mu337 is dominant for ALM and Q-cell migrations. We mapped
mu337 and identified it as a new, viable allele of
pat-3, a b integrin subunit. This finding was intriguing because Rho GTPases have been implicated in integrin signalling in vertebrate systems. Based on the strong phenotypic similarity between the
mig-2(
rh17) and
pat-3(
mu337) phenotypes, we hypothesize that
mig-2 may act in an integrin-mediated pathway to regulate cell motility. In cells such as CAN and HSN which are only perturbed by activated
mig-2 alleles,
mig-2 may have a redundant function, perhaps in a GTPase "signalling cassette." Since
mig-2 is required for wild-type migration in the QR lineage, there may be no redundant pathway--or the Q cells may be more sensitive to the level of GTPase signalling.
mig-2 appears to be active in non-migratory processes as well. Loss of
mig-2 function partially suppresses the Muv phenotype of
let-60gf, suggesting that
mig-2 may have a redundant function in Ras signalling. In addition,
mig-2 may play a role in muscle organization, perhaps by interacting with
unc-89 (see abstract by T. Tinley and G. Benian, this meeting). To identify new genes that act in the same pathway as or in parallel to
mig-2, we have isolated suppressors of activated
mig-2 mutants by EMS mutagenesis and by screening in a
mut-7 background. Interestingly, different mutations suppress different aspects of the activated
mig-2 phenotype. For example, the suppressor
mu144 suppresses all of the activated phenotypes except for the Q migration defect, essentially reverting an activated
mig-2 mutant to a null. Characterization of
mu144 and other suppressors should identify more of
mig-2's apparently diverse signalling partners.