PMID- 17296787
OWN - NLM
STAT- MEDLINE
DCOM- 20070326
LR  - 20181113
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 204
IP  - 2
DP  - 2007 Feb 19
TI  - Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV 
      to the proteasome in dendritic cells.
PG  - 421-30
AB  - Dendritic cells (DCs) capture and internalize human immunodeficiency virus 
      (HIV)-1 through C-type lectins, including DC-SIGN. These cells mediate efficient 
      infection of T cells by concentrating the delivery of virus through the 
      infectious synapse, a process dependent on the cytoplasmic domain of DC-SIGN. 
      Here, we identify a cellular protein that binds specifically to the cytoplasmic 
      region of DC-SIGN and directs internalized virus to the proteasome. This cellular 
      protein, leukocyte-specific protein 1 (LSP1), was defined biochemically by 
      immunoprecipitation and matrix-assisted laser desorption/ionization 
      time-of-flight mass spectrometry. LSP1 is an F-actin binding protein involved in 
      leukocyte motility and found on the cytoplasmic surface of the plasma membrane. 
      LSP1 interacted specifically with DC-SIGN and other C-type lectins, but not the 
      inactive mutant DC-SIGNDelta35, which lacks a cytoplasmic domain and shows 
      altered virus transport in DCs. LSP1 diverts HIV-1 to the proteasome. 
      Down-regulation of LSP1 with specific small interfering RNAs in human DCs 
      enhanced HIV-1 transfer to T cells, and bone marrow DCs from lsp1(-/-) mice also 
      showed an increase in transfer of HIV-1(BaL) to a human T cell line. Proteasome 
      inhibitors increased retention of viral proteins in lsp1(+/+) DCs, and 
      substantial colocalization of virus to the proteasome was observed in wild-type 
      compared with LSP1-deficient cells. Collectively, these data suggest that LSP1 
      protein facilitates virus transport into the proteasome after its interaction 
      with DC-SIGN through its interaction with cytoskeletal proteins.
FAU - Smith, Alvin L
AU  - Smith AL
AD  - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, 
      National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Ganesh, Lakshmanan
AU  - Ganesh L
FAU - Leung, Kwanyee
AU  - Leung K
FAU - Jongstra-Bilen, Jenny
AU  - Jongstra-Bilen J
FAU - Jongstra, Jan
AU  - Jongstra J
FAU - Nabel, Gary J
AU  - Nabel GJ
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070212
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (LSP1 protein, human)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 3.4.21.- (Prss28 protein, mouse)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Biological Transport/physiology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Line
MH  - Cytoplasm/metabolism
MH  - Dendritic Cells/*virology
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Lectins, C-Type/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microfilament Proteins/*metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - RNA Interference
MH  - Receptors, Cell Surface/*metabolism
MH  - Serine Endopeptidases/genetics
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - T-Lymphocytes/virology
PMC - PMC2118718
EDAT- 2007/02/14 09:00
MHDA- 2007/03/27 09:00
PMCR- 2007/08/19
CRDT- 2007/02/14 09:00
PHST- 2007/02/14 09:00 [pubmed]
PHST- 2007/03/27 09:00 [medline]
PHST- 2007/02/14 09:00 [entrez]
PHST- 2007/08/19 00:00 [pmc-release]
AID - jem.20061604 [pii]
AID - 20061604 [pii]
AID - 10.1084/jem.20061604 [doi]
PST - ppublish
SO  - J Exp Med. 2007 Feb 19;204(2):421-30. doi: 10.1084/jem.20061604. Epub 2007 Feb 
      12.