PMID- 21933838
OWN - NLM
STAT- MEDLINE
DCOM- 20120308
LR  - 20220129
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 20
IP  - 24
DP  - 2011 Dec 15
TI  - The role of RPGR in cilia formation and actin stability.
PG  - 4840-50
LID - 10.1093/hmg/ddr423 [doi]
AB  - Mutations in the retinitis pigmentosa GTPase regulator (RPGR) protein cause one 
      of the most common and severe forms of inherited retinal dystrophy. In spite of 
      numerous studies, the precise function of RPGR remains unclear, as is the 
      mechanism by which RPGR mutations cause retinal degeneration. We have analysed 
      the function of RPGR by RNA interference-mediated translational suppression 
      [knockdown (KD)] using a model cellular system for studying the formation, 
      maintenance and function of primary cilia (human telomerase-immortalized retinal 
      pigmented epithelium 1 cells). We observed that RPGR-deficient cells exhibited 
      reduced numbers of cilia, slower cell cycle progression and impaired attachment 
      to fibronectin, but showed no migration defects in a wound-healing assay. RPGR KD 
      cells showed stronger actin filaments, associated with basal dysregulation of the 
      Akt, Erk1/2, focal adhesion kinase and Src signalling pathways, as well as a 20% 
      reduction in beta1-integrin receptors at the cell surface and impaired 
      fibronectin-induced signalling. Stronger actin filaments and impairment of the 
      above signalling pathways suggest a common underlying mechanism for all of the 
      cellular phenotypes observed in RPGR KD cells. Our data underline a novel 
      function for RPGR in cilia formation and in the regulation of actin stress 
      filaments, suggesting that, in the retina, it may regulate nascent photoreceptor 
      disc formation by regulating actin-mediated membrane extension.
FAU - Gakovic, Milica
AU  - Gakovic M
AD  - MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh 
      EH4 2XU, UK.
FAU - Shu, Xinhua
AU  - Shu X
FAU - Kasioulis, Ioannis
AU  - Kasioulis I
FAU - Carpanini, Sarah
AU  - Carpanini S
FAU - Moraga, Ignacio
AU  - Moraga I
FAU - Wright, Alan F
AU  - Wright AF
LA  - eng
GR  - MC_U127584475/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110920
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Actins)
RN  - 0 (Eye Proteins)
RN  - 0 (Integrin beta1)
RN  - 0 (RPGR protein, human)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
SB  - IM
MH  - Actin Cytoskeleton/metabolism
MH  - Actins/*metabolism
MH  - Animals
MH  - Cell Cycle
MH  - Cell Division
MH  - Cell Line
MH  - Cell Movement
MH  - Cell Shape
MH  - Cilia/*metabolism
MH  - Epithelial Cells/cytology/enzymology
MH  - Eye Proteins/*metabolism
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Focal Adhesions/metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Integrin beta1/metabolism
MH  - Mice
MH  - *Organogenesis
MH  - Retinal Pigment Epithelium/cytology
MH  - Signal Transduction
EDAT- 2011/09/22 06:00
MHDA- 2012/03/09 06:00
CRDT- 2011/09/22 06:00
PHST- 2011/09/22 06:00 [entrez]
PHST- 2011/09/22 06:00 [pubmed]
PHST- 2012/03/09 06:00 [medline]
AID - ddr423 [pii]
AID - 10.1093/hmg/ddr423 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2011 Dec 15;20(24):4840-50. doi: 10.1093/hmg/ddr423. Epub 2011 Sep 
      20.