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Journal article
The Actin Regulatory Protein HS1 Interacts with Arp2/3 and Mediates Efficient Neutrophil Chemotaxis
The Journal of biological chemistry, Vol.287(30), pp.25466-25477
07/20/2012
PMCID: PMC3408136
PMID: 22679023
Web of Science ID: WOS:000306651700053
Abstract
Background: HS1 is a cortactin homolog, however its role in neutrophil chemotaxis is not known.
Results: HS1 interacts with Arp2/3, regulates Vav1 and Rac signaling, and is necessary for efficient neutrophil chemotaxis.
Conclusion: HS1 tyrosine phosphorylation is critical for its interaction with Arp2/3 and efficient neutrophil chemotaxis.
Significance: This work increases our understanding of how actin regulatory proteins mediate efficient cell migration.
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.
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- Title
- The Actin Regulatory Protein HS1 Interacts with Arp2/3 and Mediates Efficient Neutrophil Chemotaxis
- Publication Details
- The Journal of biological chemistry, Vol.287(30), pp.25466-25477
- Resource Type
- Journal article
- Publisher
- Elsevier Inc
- Format
- pdf
- Grant note
- This work was supported, in whole or in part, by National Institutes of Health Grant RO1EB010039 (to A.H. and D.J.B.) and AHA Grant 10POST3230031 (to P. J. C.).
- Copyright
- ©2012 by The American Society for Biochemistry and Molecular Biology, Inc This is an Open Access article under the CC BY license.
- Identifiers
- WOS:000306651700053; 99380171296306600
- Academic Unit
- Biology; Hal Marcus College of Science and Engineering
- Language
- English