Dataset Information

Rab11 regulates cell-cell communication during collective cell movements.

ABSTRACT: Collective cell movements contribute to development and metastasis. The small GTPase Rac is a key regulator of actin dynamics and cell migration but the mechanisms that restrict Rac activation and localization in a group of collectively migrating cells are unknown. Here, we demonstrate that the small GTPases Rab5 and Rab11 regulate Rac activity and polarization during collective cell migration. We use photoactivatable forms of Rac to demonstrate that Rab11 acts on the entire group to ensure that Rac activity is properly restricted to the leading cell through regulation of cell-cell communication. In addition, we show that Rab11 binds to the actin cytoskeleton regulator Moesin and regulates its activation in vivo during migration. Accordingly, reducing the level of Moesin activity also affects cell-cell communication, whereas expressing active Moesin rescues loss of Rab11 function. Our model suggests that Rab11 controls the sensing of the relative levels of Rac activity in a group of cells, leading to the organization of individual cells in a coherent multicellular motile structure.

SUBMITTER: Ramel D

PROVIDER: S-EPMC4006229 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Rab11 regulates cell-cell communication during collective cell movements.

Ramel Damien D Wang Xiaobo X Laflamme Carl C Montell Denise J DJ Emery Gregory G

Nature cell biology 20130203 3

Collective cell movements contribute to development and metastasis. The small GTPase Rac is a key regulator of actin dynamics and cell migration but the mechanisms that restrict Rac activation and localization in a group of collectively migrating cells are unknown. Here, we demonstrate that the small GTPases Rab5 and Rab11 regulate Rac activity and polarization during collective cell migration. We use photoactivatable forms of Rac to demonstrate that Rab11 acts on the entire group to ensure that ...[more]

PMID: 23376974

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Project description:BackgroundSocial insect colonies routinely face large vertebrate predators, against which they need to mount a collective defence. To do so, honeybees use an alarm pheromone that recruits nearby bees into mass stinging of the perceived threat. This alarm pheromone is carried directly on the stinger; hence, its concentration builds up during the course of the attack. We investigate how bees react to different alarm pheromone concentrations and how this evolved response pattern leads to better coordination at the group level.ResultsWe first present a dose-response curve to the alarm pheromone, obtained experimentally. This data reveals two phases in the bees' response: initially, bees become more likely to sting as the alarm pheromone concentration increases, but aggressiveness drops back when very high concentrations are reached. Second, we apply Projective Simulation to model each bee as an artificial learning agent that relies on the pheromone concentration to decide whether to sting or not. Individuals are rewarded based on the collective performance, thus emulating natural selection in these complex societies. By also modelling predators in a detailed way, we are able to identify the main selection pressures that shaped the response pattern observed experimentally. In particular, the likelihood to sting in the absence of alarm pheromone (starting point of the dose-response curve) is inversely related to the rate of false alarms, such that bees in environments with low predator density are less likely to waste efforts responding to irrelevant stimuli. This is compensated for by a steep increase in aggressiveness when the alarm pheromone concentration starts rising. The later decay in aggressiveness may be explained as a curbing mechanism preventing worker loss.ConclusionsOur work provides a detailed understanding of alarm pheromone responses in honeybees and sheds light on the selection pressures that brought them about. In addition, it establishes our approach as a powerful tool to explore how selection based on a collective outcome shapes individual responses, which remains a challenging issue in the field of evolutionary biology.

Dataset Information

Rab11 regulates cell-cell communication during collective cell movements.

Publications

Rab11 regulates cell-cell communication during collective cell movements.

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