Pattern formation of Rho GTPases in single cell wound healing

Simon, Cory; Vaughan, Emily M.; Bement, William M.; Edelstein‐Keshet, Leah

doi:10.1091/mbc.e12-08-0634

Cited by 47 publications

(59 citation statements)

References 29 publications

(67 reference statements)

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“…Abr is recruited to the Rho zone by active Rho, where it establishes a positive feedback loop with active Rho via its GEF activity and suppresses Cdc42 via its GAP activity (**33). A mathematical model shows that Abr's involvement explains the basic features of the Rho GTPase response and makes accurate, nonintuitive predictions about pattern formation, as long as the model includes nonlinear positive feedback not only for the Rho-Abr interaction but also for Cdc42 activation (**35). The nature of the feedback to Cdc42 is unknown, but based on other systems, a loop running from Cdc42 to dynamic actin seems plausible (**36).…”

Section: Single Cell Pattern Formationmentioning

confidence: 99%

Single cell pattern formation and transient cytoskeletal arrays

Dassow

2014

Current Opinion in Cell Biology

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A major goal of developmental biology is to explain the emergence of pattern in cell layers, tissues and organs. Developmental biologists now accept that reaction diffusion-based mechanisms are broadly employed in developing organisms to direct pattern formation. Here we briefly consider these mechanisms and then apply some of the concepts derived from them to several processes that occur in single cells: wound repair, yeast budding, and cytokinesis. Two conclusions emerge from this analysis: first, there is considerable overlap at the level of general mechanisms between developmental and single cell pattern formation; second, dynamic structures based on the actin cytoskeleton may be far more ordered than is generally recognized.

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Section: Single Cell Pattern Formationmentioning

confidence: 99%

Single cell pattern formation and transient cytoskeletal arrays

Dassow

2014

Current Opinion in Cell Biology

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“…2A is the cross-talk between components that participate in the activation and inhibition loops. The cross-talk between the RhoGTPases and other signaling molecules has been well-documented in cell motility and wound healing (43)(44)(45). For example, Rho activates Rho-kinase (ROCK), which then regulates cofilin activity through LIM domain kinase and MLCK activity.…”

Section: Resultsmentioning

confidence: 99%

Paradoxical signaling regulates structural plasticity in dendritic spines

Rangamani

Levy

Khan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Transient spine enlargement (3-to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.CaMKII | dendritic spine | actin

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“…However, numerous questions remain unanswered regarding GTPase regulation. Recently, several successful efforts were made (Jilkine et al, 2007;Simon et al, 2013), for which the mutual exclusion between Rac/Cdc42 with Rho was taken into account, with each member undergoing self-cycle between inactive GDP-bound and active GTP-bound states. A characteristic output of these models is a spatial segregation phenomenon: Rac and Cdc42 concentrations are high at the front end of a cell and low at the back of a cell, while Rho localizes in a complementary pattern.…”

Section: Discussionmentioning

confidence: 99%