PMID- 25712868
OWN - NLM
STAT- MEDLINE
DCOM- 20150831
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1853
IP  - 5
DP  - 2015 May
TI  - Homer proteins mediate the interaction between STIM1 and Cav1.2 channels.
PG  - 1145-53
LID - S0167-4889(15)00064-6 [pii]
LID - 10.1016/j.bbamcr.2015.02.014 [doi]
AB  - STIM1 is a ubiquitous Ca2+ sensor of the intracellular, agonist-sensitive, Ca2+ 
      stores that communicates the filling state of the Ca2+ compartments to plasma 
      membrane store-operated Ca2+ (SOC) channels. STIM1 has been presented as a point 
      of convergence between store-operated and voltage-operated Ca2+ influx, both 
      inducing activation of SOC channels while suppressing Cav1.2 channels. Here we 
      report that Homer proteins play a relevant role in the communication between 
      STIM1 and Cav1.2 channels. HEK-293 cells transiently expressing Cav1.2 channel 
      subunits alpha1, beta2 and alpha2delta-1 exhibited a significant Ca2+ entry upon treatment with 
      a high concentration of KCl. In Cav1.2-expressing cells, treatment with 
      thapsigargin (TG), to induce passive discharge of the intracellular Ca2+ stores, 
      resulted in Ca2+ influx that was significantly greater than in cells not 
      expressing Cav1.2 channels, a difference that was abolished by nifedipine and 
      diltiazem. Treatment with TG induces co-immunoprecipitation of Homer1 with STIM1 
      and the Cav1.2 alpha1 subunit. Impairment of Homer function by introduction of the 
      synthetic PPKKFR peptide into cells, which emulates the proline-rich sequences of 
      the PPXXF motif, or using siRNA Homer1, reduced the association of STIM1 and the 
      Cav1.2 alpha1 subunit. These findings indicate that Homer is important for the 
      association between both proteins. Finally, treatment with siRNA Homer1 or the 
      PPKKFR peptide enhanced the nifedipine-sensitive component of TG response in 
      Cav1.2-expressing cells. Altogether, these findings provide evidence for a new 
      role of Homer1 supporting the regulation of Cav1.2 channels by STIM1.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Dionisio, Natalia
AU  - Dionisio N
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Smani, Tarik
AU  - Smani T
AD  - Department of Medical Physiology and Biophysic, Institute of Biomedicine of 
      Sevilla, Sevilla, Spain.
FAU - Woodard, Geoffrey E
AU  - Woodard GE
AD  - Department of Surgery, Uniformed Services University of the Health Sciences, 
      Bethesda, MD, USA.
FAU - Castellano, Antonio
AU  - Castellano A
AD  - Department of Medical Physiology and Biophysic, Institute of Biomedicine of 
      Sevilla, Sevilla, Spain.
FAU - Salido, Gines M
AU  - Salido GM
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Rosado, Juan A
AU  - Rosado JA
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain. Electronic address: jarosado@unex.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150221
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Carrier Proteins)
RN  - 0 (HOMER1 protein, human)
RN  - 0 (Homer Scaffolding Proteins)
RN  - 0 (Homer1 protein, rat)
RN  - 0 (L-type calcium channel alpha(1C))
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptides)
RN  - 0 (Protein Subunits)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 67526-95-8 (Thapsigargin)
RN  - EE92BBP03H (Diltiazem)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Channels, L-Type/*metabolism
MH  - Carrier Proteins/*metabolism
MH  - Diltiazem/pharmacology
MH  - HEK293 Cells
MH  - Homer Scaffolding Proteins
MH  - Humans
MH  - Immunoprecipitation
MH  - Intracellular Space/drug effects/metabolism
MH  - Membrane Proteins/*metabolism
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/*metabolism
MH  - Nifedipine/pharmacology
MH  - Peptides/chemistry/pharmacology
MH  - Protein Binding/drug effects
MH  - Protein Subunits/metabolism
MH  - Rabbits
MH  - Rats
MH  - Stromal Interaction Molecule 1
MH  - Thapsigargin/pharmacology
OTO - NOTNLM
OT  - Ca(2+) entry
OT  - Ca(v)1.2 channels
OT  - Homer1
OT  - Nifedipine
OT  - Protein-protein interactions
OT  - STIM1
EDAT- 2015/02/26 06:00
MHDA- 2015/09/01 06:00
CRDT- 2015/02/26 06:00
PHST- 2014/11/06 00:00 [received]
PHST- 2015/01/28 00:00 [revised]
PHST- 2015/02/16 00:00 [accepted]
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
AID - S0167-4889(15)00064-6 [pii]
AID - 10.1016/j.bbamcr.2015.02.014 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2015 May;1853(5):1145-53. doi: 
      10.1016/j.bbamcr.2015.02.014. Epub 2015 Feb 21.