Abstract:
:Chemoattractants induce neutrophil polarization through localized polymerization of F-actin at the leading edge. The suppression of rear and lateral protrusions is required for efficient chemotaxis and involves the temporal and spatial segregation of signaling molecules. We have previously shown that the intracellular calcium-dependent protease calpain is required for cell migration and is involved in regulating neutrophil chemotaxis. Here, we show that primary neutrophils and neutrophil-like HL-60 cells express both calpain 1 and calpain 2 and that chemoattractants induce the asymmetric recruitment of calpain 2, but not calpain 1, to the leading edge of polarized neutrophils and differentiated HL-60 cells. Using time-lapse microscopy, we show that enrichment of calpain 2 at the leading edge occurs during early pseudopod formation and that its localization is sensitive to changes in the chemotactic gradient. We demonstrate that calpain 2 is recruited to lipid rafts and that cholesterol depletion perturbs calpain 2 localization, suggesting that its enrichment at the front requires proper membrane organization. Finally, we show that catalytic activity of calpain is required to limit pseudopod formation in the direction of chemoattractant and for efficient chemotaxis. Together, our findings identify calpain 2 as a novel component of the frontness signal that promotes polarization during chemotaxis.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Nuzzi PA,Senetar MA,Huttenlocher Adoi
10.1091/mbc.e06-09-0876subject
Has Abstractpub_date
2007-03-01 00:00:00pages
795-805issue
3eissn
1059-1524issn
1939-4586pii
E06-09-0876journal_volume
18pub_type
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journal_title:Molecular biology of the cell
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journal_title:Molecular biology of the cell
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-10-1084
更新日期:2009-06-01 00:00:00
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journal_title:Molecular biology of the cell
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pub_type: 杂志文章
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