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2017 ; 114
(37
): E7727-E7736
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Shear force-based genetic screen reveals negative regulators of cell adhesion and
protrusive activity
#MMPMID28847951
Lampert TJ
; Kamprad N
; Edwards M
; Borleis J
; Watson AJ
; Tarantola M
; Devreotes PN
Proc Natl Acad Sci U S A
2017[Sep]; 114
(37
): E7727-E7736
PMID28847951
show ga
The model organism Dictyostelium discoideum has greatly facilitated our
understanding of the signal transduction and cytoskeletal pathways that govern
cell motility. Cell-substrate adhesion is downstream of many migratory and
chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor
PTEN show strongly impaired migratory activity and adhere strongly to their
substrates. We reasoned that other regulators of migration could be obtained
through a screen for overly adhesive mutants. A screen of restriction
enzyme-mediated integration mutagenized cells yielded numerous mutants with the
desired phenotypes, and the insertion sites in 18 of the strains were mapped.
These regulators of adhesion and motility mutants have increased adhesion and
decreased motility. Characterization of seven strains demonstrated decreased
directed migration, flatness, increased filamentous actin-based protrusions, and
increased signal transduction network activity. Many of the genes share homology
to human genes and demonstrate the diverse array of cellular networks that
function in adhesion and migration.