Chemogenetic Control of Protein Localization and Mammalian Cell Signaling by SLIPT

CLAMP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the Xenopus ciliated epithelia

The Journal of Cell Biology ◽

10.1083/jcb.201706058 ◽

2018 ◽

Vol 217 (5) ◽

pp. 1633-1641 ◽

Cited By ~ 13

Author(s):

Sun K. Kim ◽

Siwei Zhang ◽

Michael E. Werner ◽

Eva J. Brotslaw ◽

Jennifer W. Mitchell ◽

...

Keyword(s):

Cell Division ◽

Epithelial Cells ◽

Cell Signaling ◽

Cell Polarity ◽

Planar Cell Polarity ◽

Protein Localization ◽

Apical Cell ◽

Cell Cortex ◽

Pcp Signaling ◽

Cell Cell

Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell–cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division. Additionally, depletion of CLAMP leads to a loss of the atypical cadherin-like molecule Celrs2, suggesting that CLAMP facilitates the stabilization of junctional interactions responsible for proper PCP protein localization. Depletion of CLAMP also affects the polarized organization of MTs. We hypothesize that CLAMP facilitates the establishment of cell polarity and promotes the asymmetric accumulation of MTs downstream of the establishment of proper PCP.

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Quantitative Models of Mammalian Cell Signaling Pathways

Science Signaling ◽

10.1126/stke.17tr1 ◽

2008 ◽

Vol 1 (7) ◽

pp. tr1-tr1

Author(s):

R. Iyengar

Keyword(s):

Cell Signaling ◽

Signaling Pathways ◽

Mammalian Cell ◽

Quantitative Models ◽

Cell Signaling Pathways

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Mapping paths: new approaches to dissect eukaryotic signaling circuitry

F1000Research ◽

10.12688/f1000research.8818.1 ◽

2016 ◽

Vol 5 ◽

pp. 1853

Author(s):

Nebibe Mutlu ◽

Anuj Kumar

Keyword(s):

Cell Signaling ◽

Protein Interactions ◽

Protein Localization ◽

Specific Protein ◽

Cellular Growth ◽

Intracellular Signals ◽

Allele Specific ◽

Coordinate Changes ◽

And Function ◽

Computational Analyses

Eukaryotic cells are precisely “wired” to coordinate changes in external and intracellular signals with corresponding adjustments in the output of complex and often interconnected signaling pathways. These pathways are critical in understanding cellular growth and function, and several experimental trends are emerging with applicability toward more fully describing the composition and topology of eukaryotic signaling networks. In particular, recent studies have implemented CRISPR/Cas-based screens in mouse and human cell lines for genes involved in various cell growth and disease phenotypes. Proteomic methods using mass spectrometry have enabled quantitative and dynamic profiling of protein interactions, revealing previously undiscovered complexes and allele-specific protein interactions. Methods for the single-cell study of protein localization and gene expression have been integrated with computational analyses to provide insight into cell signaling in yeast and metazoans. In this review, we present an overview of exemplary studies using the above approaches, relevant for the analysis of cell signaling and indeed, more broadly, for many modern biological applications.

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