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First published online 13 October 2009
doi: 10.1242/jcs.049346

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The transmembrane protein CBP plays a role in transiently anchoring small clusters of Thy-1, a GPI-anchored protein, to the cytoskeleton

¹ Department of Cell and Developmental Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA
² National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20815, USA
³ CRBM, CNRS UMR5237, Universities of Montpellier I & II, 1919 route de Mende, 34293 Montpellier, France

^* Author for correspondence (frap{at}med.unc.edu)

Accepted 24 August 2009

It remains unclear how GPI-anchored proteins (GPIAPs), which lack cytoplasmic domains, transduce signals triggered by specific ligation. Such signal transduction has been speculated to require the ligated GPIAP to associate with membrane-spanning proteins that communicate with obligate cytoplasmic proteins. Transient anchorage of crosslinked proteins on the cell surface was previously characterized by single-particle tracking, and temporary association with the actin cytoskeleton was hypothesized to cause regulated anchorage. GPIAPs, such as Thy-1, require clustering, cholesterol and Src-family kinase (SFK) activity to become transiently anchored. By contrast, a transmembrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which has a PDZ-binding motif in its cytoplasmic C-terminus that binds the ERM adaptor EBP50, exhibits anchorage that strictly requires EBP50 but has little dependence on cholesterol or SFK. We hypothesized that a transmembrane protein would be required to mediate the linkage between Thy-1 and the cytoskeleton. Here, we present evidence, obtained by shRNA knockdown, that the transmembrane protein Csk-binding protein (CBP) plays an obligatory role in the transient anchorage of Thy1. Furthermore, either a dominant-negative form of CBP that did not bind EBP50 or a dominant-negative EBP50 drastically reduced transient anchorage of Thy-1, indicating the involvement of this adaptor. Finally, we speculate on the role of phosphorylation in the regulation of transient anchorage.

Key words: Lipid rafts, Signal transduction, Single-particle tracking, GPI-anchored proteins, CFTR, Thy-1, Cytoskeleton

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