580 581

Cited 109 times in

Homer 1 Mediates Store- and Inositol 1,4,5-Trisphosphate Receptor-dependent Translocation and Retrieval of TRPC3 to the Plasma Membrane

Authors
 Joo Young Kim  ;  Weizong Zeng  ;  Kirill Kiselyov  ;  Joseph P. Yuan  ;  Marlin H. Dehoff  ;  Katsuhiko Mikoshiba  ;  Paul F. Worley  ;  Shmuel Muallem 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.281(43) : 32540-32549, 2006 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2006
MeSH
Animals ; Carrier Proteins/metabolism* ; Cell Culture Techniques ; Cell Line ; Cell Membrane/metabolism* ; Collagenases/pharmacology ; Homer Scaffolding Proteins ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism* ; Mice ; Models, Biological ; Pancreas/cytology ; Pancreas/drug effects ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Cytoplasmic and Nuclear/physiology* ; TRPC Cation Channels/genetics ; TRPC Cation Channels/metabolism* ; TRPC Cation Channels/physiology* ; Trypsin/pharmacology
Abstract
Store-operated Ca2+ channels (SOCs) mediate receptor-stimulated Ca2+ influx. Accumulating evidence indicates that members of the transient receptor potential (TRP) channel family are components of SOCs in mammalian cells. Agonist stimulation activates SOCs and TRP channels directly and by inducing translocation of channels in intracellular vesicles to the plasma membrane (PM). The mechanism of TRP channel translocation in response to store depletion and agonist stimulation is not known. Here we use TRPC3 as a model to show that IP3 and the scaffold Homer 1 (H1) regulate the rate of translocation and retrieval of TRPC3 from the PM. In resting cells, TRPC3 exists in TRPC3-H1b/c-IP3Rs complexes that are located in part at the PM and in part in intracellular vesicles. Binding of IP3 to the IP3Rs dissociates the interaction between IP3Rs and H1 but not between H1 and TRPC3 to form IP3Rs-TRPC3-H1b/c. TIRFM and biotinylation assays show robust receptor- and store-dependent translocation of the TRPC3 to the PM and their retrieval upon termination of cell stimulation. The translocation requires depletion of stored Ca2+ and is prevented by inhibition of the IP3Rs. In HEK293, dissociating the H1b/c-IP3R complex with H1a results in TRPC3 translocation to the PM, where it is spontaneously active. The TRPC3-H1b/c-IP3Rs complex is reconstituted by infusing H1c into these cells. Reconstitution is inhibited by IP3. Deletion of H1 in mice markedly reduces the rates of translocation and retrieval of TRPC3. Conversely, infusion of H1c into H1-/- cells eliminates spontaneous channel activity and increases the rate of channel activation by agonist stimulation. The effects of H1c are inhibited by IP3. These findings together with our earlier studies demonstrating gating of TRPC3 by IP3Rs were used to develop a model in which assembly of the TRPC3-H1b/c-IP3Rs complexes by H1b/c mediates both the translocation of TRPC3-containing vesicles to the PM and gating of TRPC3 by IP3Rs.
Files in This Item:
T200601716.pdf Download
DOI
10.1074/jbc.M602496200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/110735
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links