Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-4-5
pubmed:abstractText
Dendritic cells (DCs) are professional APCs that reside in peripheral tissues and survey the body for pathogens. Upon activation by inflammatory signals, DCs undergo a maturation process and migrate to lymphoid organs, where they present pathogen-derived Ags to T cells. DC migration depends on tight regulation of the actin cytoskeleton to permit rapid adaptation to environmental cues. We investigated the role of hematopoietic lineage cell-specific protein 1 (HS1), the hematopoietic homolog of cortactin, in regulating the actin cytoskeleton of murine DCs. HS1 localized to lamellipodial protrusions and podosomes, actin-rich structures associated with adhesion and migration. DCs from HS1(-/-) mice showed aberrant lamellipodial dynamics. Moreover, although these cells formed recognizable podosomes, their podosome arrays were loosely packed and improperly localized within the cell. HS1 interacts with Wiskott-Aldrich syndrome protein (WASp), another key actin-regulatory protein, through mutual binding to WASp-interacting protein. Comparative analysis of DCs deficient for HS1, WASp or both proteins revealed unique roles for these proteins in regulating podosomes with WASp being essential for podosome formation and with HS1 ensuring efficient array organization. WASp recruitment to podosome cores was independent of HS1, whereas HS1 recruitment required Src homology 3 domain-dependent interactions with the WASp/WASp-interacting protein heterodimer. In migration assays, the phenotypes of HS1- and WASp-deficient DCs were related, but distinct. WASp(-/y) DCs migrating in a chemokine gradient showed a large decrease in velocity and diminished directional persistence. In contrast, HS1(-/-) DCs migrated faster than wild-type cells, but directional persistence was significantly reduced. These studies show that HS1 functions in concert with WASp to fine-tune DC cytoarchitecture and direct cell migration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4805-18
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:21398607-Actins, pubmed-meshheading:21398607-Animals, pubmed-meshheading:21398607-Antigen Presentation, pubmed-meshheading:21398607-Blotting, Western, pubmed-meshheading:21398607-Bone Marrow Cells, pubmed-meshheading:21398607-Cell Movement, pubmed-meshheading:21398607-Cells, Cultured, pubmed-meshheading:21398607-Chemotaxis, pubmed-meshheading:21398607-Cytoskeleton, pubmed-meshheading:21398607-Dendritic Cells, pubmed-meshheading:21398607-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:21398607-Green Fluorescent Proteins, pubmed-meshheading:21398607-Mice, pubmed-meshheading:21398607-Mice, Inbred C57BL, pubmed-meshheading:21398607-Mice, Knockout, pubmed-meshheading:21398607-Microscopy, Fluorescence, pubmed-meshheading:21398607-Protein Binding, pubmed-meshheading:21398607-Pseudopodia, pubmed-meshheading:21398607-Wiskott-Aldrich Syndrome Protein
pubmed:year
2011
pubmed:articleTitle
Hematopoietic lineage cell-specific protein 1 functions in concert with the Wiskott-Aldrich syndrome protein to promote podosome array organization and chemotaxis in dendritic cells.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article