PMID- 29796181
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230818
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 33
DP  - 2018 May 1
TI  - RPGR protein complex regulates proteasome activity and mediates store-operated 
      calcium entry.
PG  - 23183-23197
LID - 10.18632/oncotarget.25259 [doi]
AB  - Ciliopathies are a group of genetically heterogeneous disorders, characterized by 
      defects in cilia genesis or maintenance. Mutations in the RPGR gene and its 
      interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function 
      of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, 
      RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton 
      organization. The actin cytoskeleton rearrangement is regulated by the small 
      GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was 
      upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, 
      RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 
      proteins, the core components of the PCP pathway, due to impaired proteasomal 
      activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an 
      inhibitor of sarcoendoplasmic reticulum Ca(2+)- ATPases, showed impaired 
      store-operated Ca(2+) entry (SOCE), which is mediated by STIM1 and Orai1 
      proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion 
      in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR 
      protein complex is required for regulating proteasomal activity and for 
      modulating SOCE, which may contribute to the ciliopathy phenotype.
FAU - Patnaik, Sarita Rani
AU  - Patnaik SR
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
AD  - Institute of Molecular Physiology, Johannes Gutenberg-Universitat Mainz, D-55128 
      Mainz, Germany.
FAU - Zhang, Xun
AU  - Zhang X
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
FAU - Biswas, Lincoln
AU  - Biswas L
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
FAU - Akhtar, Saeed
AU  - Akhtar S
AD  - Cornea Research Chair, Department of Optometry, King Saud University, Riyadh 
      11433, Kingdom of Saudi Arabia.
FAU - Zhou, Xinzhi
AU  - Zhou X
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
FAU - Kusuluri, Deva Krupakar
AU  - Kusuluri DK
AD  - Institute of Molecular Physiology, Johannes Gutenberg-Universitat Mainz, D-55128 
      Mainz, Germany.
FAU - Reilly, James
AU  - Reilly J
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
FAU - May-Simera, Helen
AU  - May-Simera H
AD  - Institute of Molecular Physiology, Johannes Gutenberg-Universitat Mainz, D-55128 
      Mainz, Germany.
FAU - Chalmers, Susan
AU  - Chalmers S
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences, University of 
      Strathclyde, Glasgow G4 0RE, Scotland.
FAU - McCarron, John G
AU  - McCarron JG
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences, University of 
      Strathclyde, Glasgow G4 0RE, Scotland.
FAU - Shu, Xinhua
AU  - Shu X
AD  - Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, 
      Scotland.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20180501
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5955404
OTO - NOTNLM
OT  - RPGR complex
OT  - actin cytoskeleton
OT  - ciliopathy
OT  - endoplasmic reticulum
OT  - store-operated Ca2+ entry
COIS- CONFLICTS OF INTEREST No conflicts of interest were declared.
EDAT- 2018/05/26 06:00
MHDA- 2018/05/26 06:01
PMCR- 2018/05/01
CRDT- 2018/05/26 06:00
PHST- 2017/12/11 00:00 [received]
PHST- 2018/04/07 00:00 [accepted]
PHST- 2018/05/26 06:00 [entrez]
PHST- 2018/05/26 06:00 [pubmed]
PHST- 2018/05/26 06:01 [medline]
PHST- 2018/05/01 00:00 [pmc-release]
AID - 25259 [pii]
AID - 10.18632/oncotarget.25259 [doi]
PST - epublish
SO  - Oncotarget. 2018 May 1;9(33):23183-23197. doi: 10.18632/oncotarget.25259. 
      eCollection 2018 May 1.