CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4‑activated MEK/ERK and PI3K/AKT pathways

Tian, Yongyang; Yin, Hong; Deng, Xia; Tang, Beichuan; Ren, Xianjun; Jiang, Tao

doi:10.3892/mmr.2018.9444

Cited by 27 publications

(31 citation statements)

References 33 publications

(38 reference statements)

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“…PI3K can also be activated directly by the Gβγ dimer (134), and PI3K catalytic subunits have a Ras-binding domain, which can be recognized by small GTPases (such as Ras). Both, the PI3K signaling cascade, which includes Akt and mTOR proteins, and the MAPK pathway, have important roles in actin reorganization and cell migration (53, 135, 136).…”

Section: Cxcl12-mediated Signaling Pathwaysmentioning

confidence: 99%

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

et al. 2019

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Chemokine receptors are members of the G protein-coupled receptor superfamily. These receptors are intimately involved in cell movement, and thus play a critical role in several physiological and pathological situations that require the precise regulation of cell positioning. CXCR4 is one of the most studied chemokine receptors and is involved in many functions beyond leukocyte recruitment. During embryogenesis, it plays essential roles in vascular development, hematopoiesis, cardiogenesis, and nervous system organization. It has been also implicated in tumor progression and autoimmune diseases and, together with CD4, is one of the co-receptors used by the HIV-1 virus to infect immune cells. In contrast to other chemokine receptors that are characterized by ligand promiscuity, CXCR4 has a unique ligand—stromal cell-derived factor-1 (SDF1, CXCL12). However, this ligand also binds ACKR3, an atypical chemokine receptor that modulates CXCR4 functions and is overexpressed in multiple cancer types. The CXCL12/CXCR4/ACKR3 axis constitutes a potential therapeutic target for a wide variety of inflammatory diseases, not only by interfering with cell migration but also by modulating immune responses. Thus far, only one antagonist directed against the ligand-binding site of CXCR4, AMD3100, has demonstrated clinical relevance. Here, we review the role of this ligand and its receptors in different autoimmune diseases.

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Section: Cxcl12-mediated Signaling Pathwaysmentioning

confidence: 99%

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

et al. 2019

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“…More recently, the nervous system vasculature has been identified as a critical substrate for guiding OPC migration via a molecular interaction that is dependent on Wnt pathway activated expression of Cxcr4 ( chemokine receptor 4 ) in OPCs and that, on the endothelial site, likely involves the presence of the Cxcr4 ligand Sdf1/Cxcl12 (stromal cell‐derived factor 1/C‐X‐C motif chemokine 12; Banisadr et al, ; Dziembowska et al, ; Tian et al, ; Tsai et al, ). Interestingly, tightly regulated interactions between Cxcr4 and the actin cytoskeleton have been assigned crucial functions during leucocytes migration and the reorganization of the actin cytoskeleton at the protrusive leading edge (Martinez‐Munoz et al, ; Okabe, Fukuda, & Broxmeyer, ).…”

Section: The Growth Cone and Its Actin Cytoskeleton As A Driver Of Dymentioning

confidence: 99%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and premyelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon.Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination. K E Y W O R D Sactin cytoskeleton, growth cone, migration, myelination, oligodendrocyte

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“…CXCR4 mediates intracellular signaling through a classical heterotrimeric G-protein, composed of Gα i , Gβ, and Gγ subunits. The Gα i monomer inhibits adenylyl cyclase activity and triggers MAPK and PI3K pathway activation [18], whereas the Gβγ dimer induces intracellular calcium mobilization through the activation of phospholipase C. Recent evidence also points towards an influence of LASP1 on the PI3K/AKT pathway, one of the most frequently dysregulated signals in cancer [19]. This pathway is initiated by receptor tyrosine kinase (RTK) or G-protein coupled receptor activation, like CXCR4, thus inducing phosphorylation of PIP2 to PIP3 by PI3K, thereby recruiting AKT1 and phosphoinositide-dependent kinase (PDK1) to the plasma membrane, where AKT1 is phosphorylated by PDK1 at T308.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

Butt

Stempfle

Lister

et al. 2020

Cells

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The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.

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CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4‑activated MEK/ERK and PI3K/AKT pathways

Cited by 27 publications

References 33 publications

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

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