Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of Gβγ have been identified, few Gα effectors are known. Gα effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell polarity and cytoskeletal reorganization functioning to directly link Gα activation to monomeric G-protein signaling.

Chemotaxis, or directional movement towards an extracellular gradient of chemicals, is necessary for processes as diverse as finding nutrients, the immune response, metastasis and wound healing. Activation of G-protein coupled receptors (GPCRs) is at the very base of the chemotactic signaling pathway. Chemotaxis starts with binding of the chemoattractant to GPCRs at the cell-surface, which finally leads to major changes in the cytoskeleton and directional cell movement towards the chemoattractant. Many chemotaxis pathways that are directly regulated by Gβγ have been identified and studied extensively; however, whether Gα is just a handle that regulates the release of Gβγ or whether Gα has its own set of distinct chemotactic effectors, is only beginning to be understood. In this review, we will discuss the different levels of regulation in GPCR signaling and the downstream pathways that are essential for proper chemotaxis.

The directional movement toward extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways. Recently, several labs have used extensive and efficient proteomic approaches to further unravel this dynamic signaling network. Together these studies showed the critical role of the interplay between heterotrimeric G-protein subunits and monomeric G proteins in regulating cytoskeletal rearrangements during chemotaxis. Here we highlight how these proteomic studies have provided greater insight into the mechanisms by which the heterotrimeric G protein cycle is regulated, how heterotrimeric G proteins-induced symmetry breaking is mediated through small G protein signaling, and how symmetry breaking in G protein signaling subsequently induces cytoskeleton rearrangements and cell migration.

ObjectiveThe purpose of the study was to explore the influencing factors of adjacent vertebral re-fracture after percutaneous vertebroplasty (PVP) for osteoporosis vertebral compression fractures (OVCFs).MethodsWe retrospectively analyzed the clinical data of 55 patients with adjacent vertebral re-fracture after PVP operation for OVCFs in our hospital from January 2016 to June 2019, they were followed up for 1 year and included in the fracture group. According to the same inclusion and exclusion criteria, we collected the clinical data of 55 patients with OVCFs without adjacent vertebral re-fracture after PVP in the same period and included them in the non-fracture group. We performed univariate and multivariate logistic regression analysis on the influencing factors of adjacent vertebral re-fracture in patients with OVCFs after PVP.ResultsThere were significant differences in body mass index (BMI), bone mineral density (BMD) T-value, amount of bone cement injected, bone cement leakage, history of glucocorticoid use, cross-sectional area (CSA), cross-sectional area asymmetry (CSAA), fat infiltration rate (FIR), and fat infiltration rate asymmetry (FIRA) of lumbar posterior group muscles [multifidus (MF) and erector spinae (ES)] between the two groups (p < 0.05). There was no significant difference in sex, age, or time from the first fracture to operation, the CAS, CSAA, FIR, and FIRA of psoas major (PS) between the two groups (p > 0.05). Multivariate logistic regression showed that a higher dose of bone cement, greater CSAA and FIR of multifidus, and higher CSAA of erector spinae were independent risk factors for recurrent fractures of adjacent vertebrae after PVP.ConclusionThere are many risk factors for recurrent vertebral fracture after PVP in patients with OVCFs, and degeneration of paraspinal muscles (especially posterior lumbar muscles) may be one of the risks.

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