title: An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration.
abstract: It is generally believed that cytoskeletal activities drive random cell migration, whereas signal transduction events initiated by receptors regulate the cytoskeleton to guide cells. However, we find that the cytoskeletal network, involving SCAR/WAVE, Arp 2/3 and actin-binding proteins, is capable of generating only rapid oscillations and undulations of the cell boundary. The signal transduction network, comprising multiple pathways that include Ras GTPases, PI(3)K and Rac GTPases, is required to generate the sustained protrusions of migrating cells. The signal transduction network is excitable, exhibiting wave propagation, refractoriness and maximal response to suprathreshold stimuli, even in the absence of the cytoskeleton. We suggest that cell motility results from coupling of 'pacemaker' signal transduction and 'idling motor' cytoskeletal networks, and various guidance cues that modulate the threshold for triggering signal transduction events are integrated to control the mode and direction of migration.
authors.affiliation: 1] Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA [2].
authors.forename: Chuan-Hsiang
authors.initials: CH
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.forename: Changji
authors.initials: C
authors.lastname: Shi
authors.forename: Pablo A
authors.identifier: 000000020840155X
authors.initials: PA
authors.lastname: Iglesias
authors.forename: Peter N
authors.initials: PN
authors.lastname: Devreotes
mesh_terms: D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D020558:GTP Phosphohydrolases