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National Institute of Environmental Health Sciences

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Publication Detail

Title: The actin regulatory protein HS1 interacts with Arp2/3 and mediates efficient neutrophil chemotaxis.

Authors: Cavnar, Peter J; Mogen, Kevin; Berthier, Erwin; Beebe, David J; Huttenlocher, Anna

Published In J Biol Chem, (2012 Jul 20)

Abstract: HS1 is an actin regulatory protein and cortactin homolog that is expressed in hematopoietic cells. Antigen receptor stimulation induces HS1 phosphorylation, and HS1 is essential for T cell activation. HS1 is also expressed in neutrophils; however, the function of HS1 in neutrophils is not known. Here we show that HS1 localizes to the neutrophil leading edge, and is phosphorylated in response to the chemoattractant formyl-Met-Leu-Phe (fMLP) in adherent cells. Using live imaging in microchannels, we show that depletion of endogenous HS1 in the neutrophil-like PLB-985 cell line impairs chemotaxis. We also find that HS1 is necessary for chemoattractant-induced activation of Rac GTPase signaling and Vav1 phosphorylation, suggesting that HS1-mediated Rac activation is necessary for efficient neutrophil chemotaxis. We identify specific phosphorylation sites that mediate HS1-dependent neutrophil motility. Expression of HS1 Y378F, Y397F is sufficient to rescue migration of HS1-deficient neutrophils, however, a triple phospho-mutant Y222F, Y378F, Y397F did not rescue migration of HS1-deficient neutrophils. Moreover, HS1 phosphorylation on Y222, Y378, and Y397 regulates its interaction with Arp2/3. Collectively, our findings identify a novel role for HS1 and its phosphorylation during neutrophil directed migration.

PubMed ID: 22679023 Exiting the NIEHS site

MeSH Terms: Actin-Related Protein 2-3 Complex/genetics; Actin-Related Protein 2-3 Complex/metabolism*; Adaptor Proteins, Signal Transducing; Amino Acid Substitution; Blood Proteins/genetics; Blood Proteins/metabolism*; Cell Line; Chemotaxis/drug effects; Chemotaxis/physiology*; Female; Humans; Male; Mutation, Missense; N-Formylmethionine Leucyl-Phenylalanine/pharmacology; Neutrophils/metabolism*; Phosphorylation/drug effects; Phosphorylation/physiology; Proto-Oncogene Proteins c-vav/genetics; Proto-Oncogene Proteins c-vav/metabolism; Signal Transduction/drug effects; Signal Transduction/physiology*; rac GTP-Binding Proteins/genetics; rac GTP-Binding Proteins/metabolism

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