CA : A Cancer Journal for Clinicians

GPR120 is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin Sensitizing Effects

Filopodia are thin, actin-rich plasma-membrane protrusions that function as antennae for cells to probe their environment. Consequently, filopodia have an important role in cell migration, neurite outgrowth and wound healing and serve as precursors for dendritic spines in neurons. The initiation and elongation of filopodia depend on the precisely regulated polymerization, convergence and crosslinking of actin filaments. The increased understanding of the functions of various actin-associated proteins during the initiation and elongation of filopodia has provided new information on the mechanisms of filopodia formation in distinct cell types.

Filopodia: molecular architecture and cellular functions

The transmission of extracellular signals to the interior of the cell is a function of plasma membrane receptors, of which the seven transmembrane receptor family is by far the largest and most versatile. Classically, these receptors stimulate heterotrimeric G proteins, which control rates of generation of diffusible second messengers and entry of ions at the plasma membrane. Recent evidence, however, indicates another previously unappreciated strategy used by the receptors to regulate intracellular signaling pathways. They direct the recruitment, activation, and scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, beta-arrestins 1 and 2. This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways.

https://science.sciencemag.org/content/sci/308/5721/512.full.pdf

Transduction of receptor signals by beta-arrestins.

Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that beta-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the beta-arrestins bring elements of specific signaling pathways into close proximity. beta-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition, investigators are discovering new roles for beta-arrestins in nuclear functions. Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.physiol.69.022405.154749

β-Arrestins and Cell Signaling

β-Arrestin2 Is Critically Involved in CXCR4-mediated Chemotaxis, and This Is Mediated by Its Enhancement of p38 MAPK Activation

Identification of β-Arrestin2 as a G Protein-Coupled Receptor-Stimulated Regulator of NF-κB Pathways

β-Arrestin Differentially Regulates the Chemokine Receptor CXCR4-mediated Signaling and Receptor Internalization, and This Implicates Multiple Interaction Sites between β-Arrestin and CXCR4

A Kinase-Independent Role for EGF Receptor in Autophagy Initiation

https://www.cell.com/trends/cell-biology/pdf/S0962-8924(06)00087-0.pdf

Yue Sun

Papers

β-Arrestin2 Is Critically Involved in CXCR4-mediated Chemotaxis, and This Is Mediated by Its Enhancement of p38 MAPK Activation

Identification of β-Arrestin2 as a G Protein-Coupled Receptor-Stimulated Regulator of NF-κB Pathways

β-Arrestin Differentially Regulates the Chemokine Receptor CXCR4-mediated Signaling and Receptor Internalization, and This Implicates Multiple Interaction Sites between β-Arrestin and CXCR4

A Kinase-Independent Role for EGF Receptor in Autophagy Initiation

Movin' on up: the role of PtdIns(4,5)P2 in cell migration