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Cytoskeleton and Nucleotide Signaling in Glioma C6 Cells

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Book cover Glioma Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 986))

Abstract

This chapter describes signaling pathways stimulated by the P2Y2 nucleotide receptor (P2Y2R), that regulate cellular processes dependent on actin cytoskeleton dynamics in glioma C6 cells. P2Y2R coupled with G-proteins, in response to ATP or UTP, regulates the level of phosphatidylinositol-4,5-bisphosphate (PIP2) which modulates a variety of actin binding proteins and is involved in calcium response and activates Rac1 and RhoA proteins. The RhoA/ROCK signaling pathway plays an important role in contractile force generation needed for the assembly of stress fibers, focal adhesions and for tail retraction during cell migration. Blocking of this pathway by a specific Rho-kinase inhibitor induces changes in F-actin organization and cell shape and decreases the level of phosphorylated myosin II and cofilin. In glioma C6 cells these changes are reversed after UTP stimulation of P2Y2R. Signaling pathways responsible for this compensation are connected with calcium signaling. Stimulation of the Rac1 mediated pathway via Go proteins needs additional interaction between αvβ5 integrins and P2Y2Rs. Rac1 activation is necessary for cofilin phosphorylation as well as integrin activation needed for focal complexes formation and stabilization of lamellipodium. Inhibition of positive Rac1 regulation prevents glioma C6 cells from recovery of control cell like morphology.

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Abbreviations

DAG:

Diacylglycerol

EGFRs:

Epidermal growth factor receptors

FAK:

Focal Adhesion Kinase

GEFs:

Guanine nucleotide exchange factors

GPCRs:

G protein-coupled receptors

IP3 :

Inositol-1,4,5-trisphosphate

LIMK:

LIM kinase

MARCKS:

Myristoylated alanine rich C-kinase substrate

MHC:

Myosin heavy chains

MLC:

Myosin light chain

MLCK:

Myosin light chain kinase

MLCP:

Myosin light chain phosphatase

P2Y2R:

P2Y2 receptor

PAK:

p21 Activated kinase

PDGFRs:

Platelet-derived growth factor receptors

PI3K:

Phosphatidylinositol 3-kinase

PIP2 :

Phosphatidylinositol-4,5-bisphosphate

PIP 5-kinase:

Phosphatidylinositol-4-phosphate 5-kinase

PIP:

Phosphoinositol phosphate

PKC:

Protein kinase C

PLC:

Phospholipase C

P-MLC:

Phosphorylated myosin light chain

PTX:

Pertussis toxin

ROCK:

Rho-associated protein kinase

SSH:

Slingshot homolog

TESK:

Testis-specific kinase

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Authors and Affiliations

  1. Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St, PL 02-093, Warsaw, Poland

    Wanda Kłopocka, Jarosław Korczyński & Paweł Pomorski

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  1. Wanda Kłopocka
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  2. Jarosław Korczyński
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  3. Paweł Pomorski
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Correspondence to Wanda Kłopocka .

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  1. , Biochemistry, Nencki Institute of Experimental Biology, Pasteur 3, Warsaw, 02-093, Poland

    Jolanta Barańska

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Kłopocka, W., Korczyński, J., Pomorski, P. (2013). Cytoskeleton and Nucleotide Signaling in Glioma C6 Cells. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 986. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4719-7_6

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