Applying Perturbation Expectation-Maximization to Protein Trajectories of Rho GTPases

Koo, Peter K.; Mochrie, S. G. J.

doi:10.1007/978-1-4939-8612-5_5

Cited by 2 publications

(4 citation statements)

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“…Identification of distinct diffusive states for BCR. In order to obtain a better understanding of the diffusive properties of BCR, we employed a systems level classification algorithm, perturbation-expectation maximization (pEM), which uses machine learning to extract the set of distinct diffusive states that best describes a diffusivity distribution 28,29 . The premise underlying pEM is that various biochemical interactions of a protein lead to a finite number of distinct diffusive behaviors (diffusive states).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, in order to obtain a better understanding of the diffusive properties of the BCR, we have employed a newly-introduced methodology, perturbationexpectation maximization (pEM), that sorts a population of trajectories into discrete diffusive states, simultaneously determining the optimal covariance values for each state. Perturbation-expectation maximization version 2 (pEM v2) was used to classify single-molecule tracks derived from different receptors 28 . To perform pEM analysis, all tracks must have the same length.…”

Section: Methodsmentioning

confidence: 99%

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WASP family proteins regulate the mobility of the B cell receptor during signaling activation

et al. 2020

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Regulation of membrane receptor mobility tunes cellular response to external signals, such as in binding of B cell receptors (BCR) to antigen, which initiates signaling. However, whether BCR signaling is regulated by BCR mobility, and what factors mediate this regulation, are not well understood. Here we use single molecule imaging to examine BCR movement during signaling activation and a novel machine learning method to classify BCR trajectories into distinct diffusive states. Inhibition of actin dynamics downstream of the actin nucleating factors, Arp2/3 and formin, decreases BCR mobility. Constitutive loss or acute inhibition of the Arp2/3 regulator, N-WASP, which is associated with enhanced signaling, increases the proportion of BCR trajectories with lower diffusivity. Furthermore, loss of N-WASP reduces the diffusivity of CD19, a stimulatory co-receptor, but not that of FcγRIIB, an inhibitory coreceptor. Our results implicate a dynamic actin network in fine-tuning receptor mobility and receptor-ligand interactions for modulating B cell signaling.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

WASP family proteins regulate the mobility of the B cell receptor during signaling activation

et al. 2020

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“…Perturbation-Expectation maximization version 2 (pEM v2) was used to classify single molecule tracks derived from different receptors 26 . To perform pEM analysis all tracks must have the same length.…”

Section: Discussionmentioning

confidence: 99%

“…In order to obtain a better understanding of the diffusive properties of the BCR, we employed a classification algorithm. Perturbation-Expectation Maximization (pEM) is a systems level analysis that uses machine learning algorithms to extract the set of distinct diffusive states that best describes a diffusivity distribution 26,27 . pEM works on the premise that for a protein, different biochemical interactions lead to different diffusive behaviors (diffusive states) and uses a classification strategy to uncover the different interactions in a statistically rigorous manner.…”

Section: Perturbation-expectation Maximization Analysis Identifies DImentioning

confidence: 99%

N-WASP regulates the mobility of the B cell receptor and co-receptors during signaling activation

Rey-Suarez

Wheatley

Koo

et al. 2019

Preprint

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Regulation of membrane receptor mobility is important in tuning the cell's response to external signals. This is particularly relevant in the context of immune receptor signaling. The binding of B cell receptors (BCR) to antigen induces B cell receptor activation. While actin dynamics and BCR signaling are known to be linked, the role of actin dynamics in modulating receptor mobility is not well understood. Here, we use single molecule imaging to examine BCR movement during signaling activation and examine the role of actin dynamics on BCR mobility. We use a novel machine learning based method to classify BCR trajectories into distinct diffusive states and show that the actin regulatory protein N-WASP regulates receptor mobility. Constitutive loss or acute inhibition of N-WASP, which is associated with enhanced signaling, leads to a predominance of BCR trajectories with lower diffusivity and is correlated with a decrease in actin dynamics. Furthermore, loss of N-WASP reduces diffusivity of CD19, a stimulatory co-receptor of the BCR but not that of unstimulated FcγRIIB, an inhibitory coreceptor. The effect of N-WASP is mirrored by inhibition of the Arp2/3 complex and formins. Our results implicate the dynamic actin network in fine-tuning receptor mobility and receptorligand interactions, thereby modulating B cell signaling.

show abstract

Applying Perturbation Expectation-Maximization to Protein Trajectories of Rho GTPases

Cited by 2 publications

References 10 publications

WASP family proteins regulate the mobility of the B cell receptor during signaling activation

WASP family proteins regulate the mobility of the B cell receptor during signaling activation

N-WASP regulates the mobility of the B cell receptor and co-receptors during signaling activation

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