PMID- 12386163
OWN - NLM
STAT- MEDLINE
DCOM- 20030227
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 52
DP  - 2002 Dec 27
TI  - Escherichia coli K1 internalization via caveolae requires caveolin-1 and protein 
      kinase Calpha interaction in human brain microvascular endothelial cells.
PG  - 50716-24
AB  - The morbidity and mortality associated with Escherichia coli K1 meningitis during 
      the neonatal period have remained significant over the last decade and are once 
      again on the rise. Transcytosis of brain microvascular endothelial cells (BMEC) 
      by E. coli within an endosome to avoid lysosomal fusion is crucial for 
      dissemination into the central nervous system. Central to E. coli internalization 
      of BMEC is the expression of OmpA (outer membrane protein A), which interacts 
      with its receptor for the actin reorganization that leads to invasion. However, 
      nothing is known about the nature of the signaling events for the formation of 
      endosomes containing E. coli K1. We show here that E. coli K1 infection of human 
      BMEC (HBMEC) results in activation of caveolin-1 for bacterial uptake via 
      caveolae. The interaction of caveolin-1 with phosphorylated protein kinase Calpha 
      (PKCalpha) at the E. coli attachment site is critical for the invasion of HBMEC. 
      Optical sectioning of confocal images of infected HBMEC indicates continuing 
      association of caveolin-1 with E. coli during transcytosis. Overexpression of a 
      dominant-negative form of caveolin-1 containing mutations in the scaffolding 
      domain blocked the interaction of phospho-PKCalpha with caveolin-1 and the E. 
      coli invasion of HBMEC, but not actin cytoskeleton rearrangement or the 
      phosphorylation of PKCalpha. The interaction of caveolin-1 with phospho-PKCalpha 
      was completely abrogated in HBMEC overexpressing dominant-negative forms of 
      either focal adhesion kinase or PKCalpha. Treatment of HBMEC with a 
      cell-permeable peptide that represents the scaffolding domain, which was coupled 
      to an antennapedia motif of a Drosophila transcription factor significantly 
      blocked the interaction of caveolin-1 with phospho-PKCalpha and E. coli invasion. 
      These results show that E. coli K1 internalizes HBMEC via caveolae and that the 
      scaffolding domain of caveolin-1 plays a significant role in the formation of 
      endosomes.
FAU - Sukumaran, Sunil K
AU  - Sukumaran SK
AD  - Division of Infectious Diseases, Children's Hospital, and the Keck School of 
      Medicine, University of Southern California, Los Angeles, California 90027, USA.
FAU - Quon, Michael J
AU  - Quon MJ
FAU - Prasadarao, Nemani V
AU  - Prasadarao NV
LA  - eng
GR  - AI40567/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021016
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antennapedia Homeodomain Protein)
RN  - 0 (CAV1 protein, human)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.13 (PRKCA protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antennapedia Homeodomain Protein
MH  - Brain/blood supply
MH  - Caveolae/*physiology
MH  - Caveolin 1
MH  - Caveolins/*metabolism
MH  - Cerebrovascular Circulation/*physiology
MH  - Endosomes/physiology
MH  - Endothelium, Vascular/*microbiology
MH  - Escherichia coli/pathogenicity/*physiology
MH  - Escherichia coli Infections/physiopathology
MH  - Homeodomain Proteins/chemistry/metabolism
MH  - Humans
MH  - Isoenzymes/*metabolism
MH  - Microcirculation/*physiology
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/chemistry/metabolism
MH  - Protein Kinase C/*metabolism
MH  - Protein Kinase C-alpha
MH  - *Transcription Factors
EDAT- 2002/10/19 04:00
MHDA- 2003/02/28 04:00
CRDT- 2002/10/19 04:00
PHST- 2002/10/19 04:00 [pubmed]
PHST- 2003/02/28 04:00 [medline]
PHST- 2002/10/19 04:00 [entrez]
AID - S0021-9258(19)31390-0 [pii]
AID - 10.1074/jbc.M208830200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Dec 27;277(52):50716-24. doi: 10.1074/jbc.M208830200. Epub 2002 
      Oct 16.