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- W2912922443 abstract "Axonal growth guidance is a tightly regulated process that involves a series of signaling receptors for axon guidance cues such as Netrin, Slit, and Semaphorin. These signals cascade through non-receptor kinases such as Abelson murine lymphosarcoma (Abl) and Src (for “sarcoma”) which results in modulation of actin/microtubule (MT) cytoskeletal dynamics. Modulation of cytoskeletal network dynamics helps steer axonal growth by varying protrusion rates and direction. Abl kinase signaling pathway has been studied extensively revealing that Abl kinase controls actin dynamics by stimulating Arp2/3 activity (through WAVE/SCAR pathway) while inhibiting Enabled (Ena). While Arp2/3 is an actin brancher, Ena is a tetrametric protein that binds strongly to actin filament plus ends in a competitive manner compared to capping proteins to accelerate filament elongation rate. Taken together, Abl is thought to activate brancher molecules increasing dendricity of actin network while preventing Ena activity reducing average filament length/turnover. Given the knowledge of signaling pathway and the essential constituents, the extent to which Abl affects branching and Ena activities remains unknown. We used an advanced active network simulation software, MEDYAN to simulate Abl kinase activity in-silico. Our simulations throw light on how protrusion rates and stability of axonal actin networks depend on concentrations of Ena and Arp2/3. We also studied how active transport that controls protrusion of actin networks. Our work lays the groundwork for addressing the challenge of computational modeling of axonal guidance in three dimensions at the level of dynamics of individual cytoskeletal components." @default.
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- W2912922443 date "2019-02-01" @default.
- W2912922443 modified "2023-09-30" @default.
- W2912922443 title "Computational Study of Abl Pathway Based Axonal Guidance" @default.
- W2912922443 doi "https://doi.org/10.1016/j.bpj.2018.11.1407" @default.
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