PMID- 21398607
OWN - NLM
STAT- MEDLINE
DCOM- 20110801
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 8
DP  - 2011 Apr 15
TI  - 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.
PG  - 4805-18
LID - 10.4049/jimmunol.1003102 [doi]
AB  - 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.
FAU - Dehring, Deborah A Klos
AU  - Dehring DA
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 
      19104, USA.
FAU - Clarke, Fiona
AU  - Clarke F
FAU - Ricart, Brendon G
AU  - Ricart BG
FAU - Huang, Yanping
AU  - Huang Y
FAU - Gomez, Timothy S
AU  - Gomez TS
FAU - Williamson, Edward K
AU  - Williamson EK
FAU - Hammer, Daniel A
AU  - Hammer DA
FAU - Billadeau, Daniel D
AU  - Billadeau DD
FAU - Argon, Yair
AU  - Argon Y
FAU - Burkhardt, Janis K
AU  - Burkhardt JK
LA  - eng
GR  - R21 AI088376/AI/NIAID NIH HHS/United States
GR  - T32 AI055428/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20110311
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Actins)
RN  - 0 (Wiskott-Aldrich Syndrome Protein)
RN  - 0 (hematopoietic lineage cell-specific protein 1, mouse)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Blotting, Western
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Chemotaxis/*immunology
MH  - Cytoskeleton/immunology/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Granulocyte Colony-Stimulating Factor/genetics/*immunology/metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - Protein Binding
MH  - Pseudopodia/immunology/metabolism
MH  - Wiskott-Aldrich Syndrome Protein/genetics/*immunology/metabolism
PMC - PMC3467106
MID - NIHMS410274
EDAT- 2011/03/15 06:00
MHDA- 2011/08/02 06:00
PMCR- 2012/10/09
CRDT- 2011/03/15 06:00
PHST- 2011/03/15 06:00 [entrez]
PHST- 2011/03/15 06:00 [pubmed]
PHST- 2011/08/02 06:00 [medline]
PHST- 2012/10/09 00:00 [pmc-release]
AID - jimmunol.1003102 [pii]
AID - 10.4049/jimmunol.1003102 [doi]
PST - ppublish
SO  - J Immunol. 2011 Apr 15;186(8):4805-18. doi: 10.4049/jimmunol.1003102. Epub 2011 
      Mar 11.